Podcasts about mesenchymal

In this enlightening conversation, Dr. Joy Kong, a triple board-certified anti-aging physician and stem cell specialist, shares her journey into the world of stem cell therapy. She discusses the profound impact of stem cells on various health conditions, their mechanisms of action, and their potential in anti-aging and longevity. Dr. Kong emphasizes the importance of understanding the science behind stem cells, addressing misconceptions, and integrating other therapies for optimal results. She also shares personal experiences and patient outcomes, highlighting the transformative power of stem cell therapy. Takeaways ✅ Stem cells can significantly improve conditions like autism and chronic pain. ✅ Mesenchymal stem cells are master signaling cells that promote repair. ✅ Misconceptions about stem cell therapy often stem from popular media. Chapters 00:00 Introduction to Dr. Joy Kong and Stem Cell Therapy 03:06 The Journey into Stem Cell Medicine 05:59 Understanding Stem Cells and Their Mechanisms 11:53 The Role of Stem Cells in Healing and Repair 15:04 Personal Experiences and Patient Outcomes 19:03 The Process of Stem Cell Treatment 23:02 The Impact of Stem Cells on Aging and Hormones 27:09 Testing and Assessing Patient Needs 29:07 Addressing Joint Issues with Stem Cells 30:57 Regrowing Cartilage: A New Hope 32:02 The Power of Stem Cells vs. Surgery 33:53 Individual Recovery: The Variability of Treatments 36:24 Understanding Treatment Costs 39:17 The Future of Stem Cells and Regenerative Medicine 46:09 Practical Tips for Slowing Aging 48:12 Debunking Myths in Stem Cell Therapy

Mesenchymal stem cells (MSCs) are multipotent adult stem cells which can differentiate into multiple cell types. MSCs can be isolated from the bone marrow, umbilical cord blood, adipose tissue, muscle, and dental pulp. However, the use of these MSCs involves a number of barriers. Human umbilical cord is limited to collection at birth. Bone marrow and fat biopsy are painful and requires general anesthesia. If only there was an easily obtainable method to collect these MSCs, like maybe even once a month, collectable in a little cup, without biopsy. WHAT… use menstrual blood you say?! Menstrual blood-derived mesenchymal stem cells (MenSCs) were first described by Meng et al. in 2007, as a novel source of MSCs. Most of the MenSC are produced by the endometrium. With the potential of multi-directional differentiation, this has spurred a list of preclinical and animal studies looking into the collection of menstrual blood for MSC processing. Men SCs have been investigated for use in Alzheimer's disease, Stroke, Spinal Cord Injury, Type I DM, wound healing, endometriosis therapy, infertility, and even Muscular Dystrophy. Is there a miracle med in menses? Listen in for details.

BUFFALO, NY- December 18, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 21 on November 22, 2024, entitled, “Anti-aging effect of extracellular vesicles from mesenchymal stromal cells on senescence-induced chondrocytes in osteoarthritis.” The study, authored by Jérémy Boulestreau, Marie Maumus, Giuliana Bertolino Minani, Christian Jorgensen, and Danièle Noël from the Institute for Regenerative Medicine and Biotherapy and Centre Hospitalier Universitaire de Montpellier, introduces a potential new therapy for osteoarthritis. This therapy uses tiny particles called extracellular vesicles (EVs), derived from fat tissue, to repair damage caused by aging cells in the joints, slowing the progression of osteoarthritis and restoring joint health. Osteoarthritis, the most common joint disorder in older adults, occurs when cartilage breaks down, leading to inflammation, stiffness, and pain. One major contributor to it is cellular senescence, a process where cells stop dividing and release harmful substances that worsen inflammation and damage joint tissues. In this study, the researchers showed that EVs from fat-derived mesenchymal stromal cells (ASC-EVs) decreased the harmful effects of senescent cells. ASC-EVs showed strong therapeutic effects in both cellular and mouse preclinical studies. They reduced inflammation and DNA damage markers in cells derived from human joints and improved cellular health. In mice with osteoarthritis, the vesicles restored joint balance, reduced cartilage damage, and preserved joint function for weeks. The findings highlight the potential of regenerative medicine, which uses the body's own mechanisms to repair damage. By targeting the aging process in joint cells, this therapy offers a breakthrough for osteoarthritis treatment. Millions of people suffering from joint pain, inflammation, and reduced mobility could benefit from this innovative approach. In the future, the researchers plan to explore ways to enhance the therapy, including whether repeated treatments could provide even longer-lasting benefits. These could lead to new options in treating osteoarthritis and other age-related conditions. “In addition to their anti-inflammatory and regenerative properties, our study confirms that ASC-EVs may be a relevant option for future clinical applications in degenerative diseases, such as OA, which are increasing with the population aging.” In conclusion, this research offers a promising regenerative therapy for osteoarthritis, with the potential to improve the quality of life for millions of older adults. DOI - https://doi.org/10.18632/aging.206158 Corresponding author - Danièle Noël - daniele.noel@inserm.fr Video short - https://www.youtube.com/watch?v=06qw2nR3ovY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206158 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Experts: Salvatore Provenzano, Medical Oncology Unit 2 - Mesenchymal and rare cancer, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy   Amalya Sargsyan, Adult Solid Tumor Clinic, Yeolyan hematology and oncology center, Yerevan, Armenia

BUFFALO, NY - December 3, 2024 – A new #review was #published in Oncotarget's Volume 15 on November 22, 2024, entitled “Mesenchymal stem cells - the secret agents of cancer immunotherapy: Promises, challenges, and surprising twists." Authored by Theia Minev, Shani Balbuena, Jaya Mini Gill, Francesco M. Marincola, Santosh Kesari, and Feng Lin from CureScience Institute, Sonata Therapeutics, and Pacific Neuroscience Institute and Providence Saint John's Health Center, this review explores the potential role of mesenchymal stem cells (MSCs) in cancer treatment. These stem cells can naturally target tumors and deliver therapeutic agents directly to cancer cells, potentially improving treatment outcomes while reducing side effects commonly associated with traditional therapies like chemotherapy. However, the authors also note significant challenges, pointing out that under certain conditions, MSCs may unintentionally promote tumor growth, highlighting the need for careful therapeutic design. MSCs are cells that can develop in different types of tissues, such as bone, fat, or cartilage, and act as natural repair agents. What makes them particularly special is their ability to respond to biological signals, like inflammation, which is often present in cancer. This enables them to locate tumors, and once there, they can deliver cancer treatments directly to the affected area. Clinical trials are already investigating MSC-based treatments for cancers such as brain tumors, melanoma, and ovarian cancer. Some results are promising, showing that MSCs can effectively deliver treatments and boost the immune system's fight against cancer. However, other trials have also revealed the complexities of MSC behavior, including variability in their effects and the potential to create conditions that support tumor growth. “This variability may be due to the tumor immune microenvironment's effects, where immune cells are inhibited by various factors, creating a conducive environment for tumor growth.” The authors also suggest that “Developing personalized MSC therapies tailored to the specific characteristics of a patient's tumor and immune system could enhance the efficacy and safety of MSC-based treatments.” Achieving this requires a deeper understanding of how MSCs interact with cancer cells and their surrounding environment. In conclusion, this review highlights both the potential and challenges of (MSCs in cancer therapy. With ongoing research and technological advancements, MSCs could become a key component of personalized cancer treatments, offering new hope for patients worldwide. DOI - https://doi.org/10.18632/oncotarget.28672 Correspondence to - Feng Lin - flin@curescience.org Video short - https://www.youtube.com/watch?v=Wwc3zDDitlc Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

n this episode, CJ dives deep into the powerful concept of neuroplasticity, the brain's ability to rewire itself and adapt through learning and experience. Neuroplasticity is not just a buzzword; it's a fundamental aspect of how we can improve cognitive performance, longevity, and overall health. CJ ties together biohacking, natural methods, and cutting-edge scientific discoveries to show how we can boost brain function, stave off aging, and optimize our physical health.Key Topics Covered:Cognitive Hacking: Improving focus, memory, creativity, and decision-making are all linked to keeping our brains flexible and sharp. CJ emphasizes that cognitive function directly impacts longevity, and brain health is a gateway to a longer, healthier life.Nootropics: CJ explores nootropics like Modafinil and its refined version, Armodafinil, as smart drugs that boost brain performance, alongside natural alternatives like cold exposure and breathing techniques, such as the Wim Hof Method.Natural Cognitive Boosters: From blueberries and dark leafy greens to mindfulness meditation, CJ offers accessible ways to keep your brain sharp without relying on synthetic compounds.Stem Cells and Aging: CJ breaks down the types of stem cells (e.g., Mesenchymal and Hematopoietic) and how they play a key role in repairing tissue and boosting the immune system. He suggests simple lifestyle changes like resistance training and intermittent fasting to naturally promote stem cell health.Muscle Growth and Anti-Aging: Maintaining muscle mass is crucial as we age. Strength training and anti-inflammatory diets rich in omega-3s can help slow down muscle degradation, while exploring the potential of follistatin for future anti-aging breakthroughs.Telomeres and Longevity: Stress management is essential for protecting telomeres, the protective caps on our DNA that shorten as we age. Practices like meditation, yoga, and spending time in nature can reduce stress and support longevity.Key Takeaways:Neuroplasticity is vital for keeping our brains flexible, and by learning new skills and habits, we keep our cognitive function sharp as we age.Natural cognitive enhancers like sleep, cold exposure, and mindfulness can be as effective as nootropics in boosting brain performance.Stem cell health can be maintained through regular exercise and intermittent fasting, which helps to boost immune function and tissue repair.Muscle maintenance is crucial for longevity; resistance training and anti-inflammatory foods can slow muscle loss and reduce inflammation.Telomere health is directly linked to stress. Reducing chronic stress through mindful practices helps protect your DNA and slow aging.5 Things You Can Start Doing Today:Practice mindfulness meditation to boost creativity, reduce stress, and support brain function.Incorporate berries and leafy greens into your diet to enhance memory and brain health.Start intermittent fasting to regenerate stem cells and improve longevity.Do strength training to maintain muscle mass and slow down the aging process.Prioritize sleep to enhance cognitive function and protect your overall health.Stay curious, and embrace a balanced approach to biohacking for a healthier, longer life!

Dr. Maya Graham interviews Drs. Josephine Hendriksen and Joachim Weischenfeldt about their recent manuscript, "Immunotherapy drives mesenchymal tumour cell state shift and TME immune response in glioblastoma patients," published online in Neuro-Oncology in May 2024.

Mesenchymal Stem Cell Therapy is a cutting-edge treatment that uses specialized cells to repair damaged tissues and reduce inflammation in the body. This is a Biohacking Reviews episode, where we review; products, supplements, health tech, practices... whatever is new and whatever we've been trying.  Dane Johnson is the CEO and founder of CrohnsColitisLifestyle. He is a board certified practitioner helping others struggling with IBD to find relief just as he has. 

Edward Park, MD, MPH, joins Integrative Practitioner Content Specialist, Avery St. Onge, to discuss mesenchymal stem cell (MSC) exosomes, their clinical applications, and how they differ from stem cells. Find us at integrativepractitioner.com or e-mail us at IPEditor@divcom.com. Theme music: "Upbeat Party" by Scott Holmes via freemusicarchive.org and "Carefree" by Kevin Mcleod via incompetech.com. About the Expert Dr. Ed Park, MD, MPH was trained at Harvard and Columbia. Beginning his career as an Ob-Gyn, he has become a key opinion leader in anti-aging and regenerative medicine with invited lectures at various conferences. He has written two books on Telomeres (Telomere Timebombs and The Telomere Miracle) and has recently completed a new one explaining exosomes entitled Exosomes: Songs of Healing. He has created a 12-hour online provider training course and treats patients in five states.

The potential of cell therapies for cerebral palsy: where are we today?Iona Novak, Madison Cb Paton, Alexandra R Griffin, Michelle Jackman, Remy K Blatch-Williams, Megan Finch-EdmondsonPMID: 37428111DOI: 10.1080/14737175.2023.2234642No abstract availableKeywords: Cerebral palsy; efficacy; inflammation; mesenchymal stem cells; safety; stem cells; umbilical cord blood.Professor Novak is the Cerebral Palsy Alliance Chair of Allied Health, and co-founder of the Cerebral Palsy Alliance Research Institute, affiliated with the Brain and Mind Centre and Faculty of Medicine and Health at The University of Sydney.

Explaining how the stem cells the guys got are DIFFERENT than the ones you can get in the United States. (3:04) Why are the U.S. regulators so slow? (9:09) Why he is so confident about the treatments he provides. (12:52) 1st vs. 2nd generation stem cells. (15:53) Where does he get his stem cells? (19:08) How does the average consumer know how to wean out the charlatans? (20:12) What are the Asian countries using stem cells for? (21:53) What do people typically notice when they do stem cell treatment for anti-aging/longevity? (23:11) More is better. (25:09) His belief on what stem cell therapy will do to us as a species. (26:20) Breaking down the stem cell treatments the guys got and the profound effects they've witnessed since.  Adam. (28:21) Sal. (47:13) Justin. (56:12) What treatment has had the biggest impact on his patients? (59:39) In the future does he see these treatments to be affordable for the masses? (1:07:25) How does he balance his personal and professional life? (1:09:35) Wrestling with manufacturing adversity with his children. (1:16:56) Related Links/Products Mentioned Unlock Longevity event – February 24, 2024 in Austin, TX ** Promo Code MINDPUMP20 - Anyone who uses this promo code will get 20% off their ticket price. ** Special Launch: Mind Pump Fitness Coaching Course ** Promo code 200OFF at checkout for $200 off ** January Promotion: New Year's Resolutions Special Offers!! New to Weightlifting Bundle | Body Transformation Bundle | New Year Extreme Intensity Bundle Body | Transformation Bundle 2.0  Mesenchymal stem/stromal cells (MSCs): origin, immune regulation, and clinical applications How iPS cells changed the world | Nature Synthetic biology   Mind Pump #1762: Tony Robbins – Life Transforming Breakthroughs In Precision Medicine Exosomal therapy—a new frontier in regenerative medicine Fecal Microbiota Transplantation: An Update on Clinical Practice Caroline GANOBIS | PhD | PhD | University of Guelph, Guelph Regenerative and Protective Actions of the GHK-Cu Peptide Sickening: How Big Pharma Broke American Health Care and How We Can Repair It – Book by John Abramson #263 - John Abramson: Big Pharma | Lex Fridman Podcast A review of vagus nerve stimulation as a therapeutic intervention The Roseto effect: a 50-year comparison of mortality rates. Mind Pump Podcast – YouTube Mind Pump Free Resources Featured Guest/People Mentioned Adeel Khan, MD (@dr.akhan) Instagram   Tony Robbins (@tonyrobbins) Instagram Caroline Ganobis, PhD Matthew Wolff (@matthew_wolff5) Instagram John Abramson (@DrJohnAbramson) Twitter Lex Fridman (@lexfridman) Twitter Inky Johnson (@InkyJohnsonMotivate) Instagram Arthur Brooks (@arthurcbrooks) Instagram

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534295v1?rss=1 Authors: Tung, V. S. K., Mathews, F., Boruk, M., Suppa, G., Foronjy, R., Pato, M., Pato, C., Knowles, J. A., Evgrafov, O. V. Abstract: Study of the neurodevelopmental molecular mechanisms of schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously used cell lines with neural progenitor properties (CNON) derived from superior or middle turbinates of patients with schizophrenia and control groups to study gene expression specific to schizophrenia. In this study, we compared single cell-RNA seq data from two CNON cell lines, one derived from an individual with schizophrenia (SCZ) and the other from a control group, with two biopsy samples from the middle turbinate (MT), also from an individual with SCZ and a control. In addition, we compared our data with previously published data from olfactory neuroepithelium (1). Our data demonstrated that CNON originated from a single cell type which is present both in middle turbinate and olfactory neuroepithelium. CNON express multiple markers of mesenchymal cells. In order to define relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data of embryonic brain (2) and found that the expression profile of CNON very closely matched one of the cell types in the embryonic brain. Finally, we evaluated differences between SCZ and control samples to assess usability and potential benefits of using single cell RNA-seq of CNON to study etiology of schizophrenia. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Stem Cell Treatment for Autoimmune diseases, Autoinmune diseases encompass a vast array of disorders in which an overactive immune system attacks its own cells and tissues leading to devastating consequences, in other words, your body damages and fights against itself. Researchers have identified greater than 100 different autoimmune diseases which are often chronic, debilitating and life threatening. Besides healing damaged tissues, stem cells have the unique ability to influence the immune system, shutting off pathological responses while preserving its ability to fight off disease. Stem cells and specifically, mesenchymal stem cells target and are attracted to inflamed tissue and start producing anti-inflammatory agents. Mesenchymal stem cells have the potential to induce the production of T regulatory cells, a type of immune cell whose function is to protect the body against immunological self-attack. #artritis #stemcelltherapy #stemcells #stemcelltransplant #stemcell #stemcelltreatment #arthritis #diabetes #diabetesmellitus #celulasmadre #guatemala #guatemalacity Stimulate Your Body To Heal Itself Naturally With The Most Advance and Comprehensive Stem Cell Treatments

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531262v1?rss=1 Authors: Wu, J., Hu, M., Jiang, H., ma, j., Xie, C., Zhang, Z., Zhou, X., Zhao, J., Tao, Z., Meng, Y., Cai, Z., Song, T., Zhang, C., Gao, R., Song, H., Gao, Y., Lin, T., Wang, C., Zhou, X. Abstract: Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism is unclear. The present study found that ovariectomized mice exhibit reductions in bone blood vessel density and expression of endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Additional data showed that endothelial cell (EC)-specific deletion of Pkm2 impair osteogenesis and worsen osteoporosis in mice. This was attributed to the impaired differentiation ability toward osteoblast of bone mesenchymal stem cells (BMSCs). Mechanistically, EC-specific deletion of Pkm2 reduce serum lactate levels secreted by ECs, which affect histone lactylation of BMSCs. We identified collagen type I alpha 2 chain, cartilage oligomeric matrix protein, ectonucleotide pyrophosphatase/phosphodiesterase 1, and transcription factor 7 like 2 as histone H3K18 lactylation-regulated osteogenic genes using joint CUT&Tag and RNA-sequencing analyses. The overexpression of PKM2 in ECs, addition of lactate, and exercise were observed to restore the phenotype of endothelial Pkm2-deficient mice. Furthermore, metabolomics of the serum indicated that osteoporosis patients showed a relatively low lactate level. The histone lactylation and related osteogenic genes of BMSCs in osteoporosis patients also decreased. In conclusion, the glycolysis of ECs fuels the differentiation of BMSCs into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis through increased serum lactate. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Commentary by Dr. Valentin Fuster

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.11.527728v1?rss=1 Authors: Manieri, E., Tie, G., Seruggia, D., Madha, S., Maglieri, A. H., Huang, K., Fujiwara, Y., Zhang, K., Orkin, S. H., McCarthy, N., Shivdasani, R. A. Abstract: PDGFRA-expressing mesenchymal cells provide a crucial niche for the self-renewing intestinal epithelium. Corresponding compartments remain unclear in the stomach, where corpus and antral glandular epithelia have similar niche dependencies but are structurally distinct from the intestine and from each other. Previous studies considered antrum and corpus as a whole and did not assess niche functions. We applied high-resolution approaches to identify regional subpopulations and niche properties of purified corpus and antral PDGFRA+ cells. PDGFRAHi sub-epithelial myofibroblasts are the principal sources of BMP ligands in both gastric segments, fall into two molecularly distinct groups that distribute asymmetrically along antral glands, and fail to support epithelial organoids in vitro. In contrast, PDGFRALo cells expressing CD55 from either segment uniquely enable corpus and antral organoid growth in the absence of other cellular or soluble factors. Our study provides detailed insights into spatial and functional organization of gastric mesenchyme and the spectrum of signaling sources. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.04.527154v1?rss=1 Authors: Liu, W., Lu, J.-Y., Wang, Y.-J., Xu, X.-x., Chen, Y.-C., Yu, S.-X., Xiang, X.-W., Chen, X.-Z., Jiu, Y., Gao, H., Sheng, M., Chen, Z.-J., Hu, X., Li, D., Maiuri, P., Huang, X., Ying, T., Xu, G.-L., Pang, D.-W., Zhang, Z.-L., Liu, B., Liu, Y.-J. Abstract: The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, high-resolution dynamics and mechanisms underlying this type of cell migration remain unclear. Here, we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo EMT-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-induced mesenchymal migration is highly dependent on the actin cytoskeleton and RhoA signaling, which is responsible for the depolymerization of robust actin stress fibers, the leading-edge protrusion formation, and the rear-edge recontraction. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.02.526815v1?rss=1 Authors: Hosseini, K., Frenzel, A., Fischer-Friedrich, E. Abstract: Epithelial-mesenchymal transition (EMT) is a key cellular transformation for many physiological and pathological processes ranging from cancer over wound healing to embryogenesis. Changes in cell migration, cell morphology and cellular contractility were identified as hallmarks of EMT. These cellular properties are known to be tightly regulated by the actin cytoskeleton. EMT-induced changes of actin-cytoskeletal regulation were demonstrated by previous reports of cell-cycle-dependent changes of actin cortex mechanics in conjunction with characteristic modifications of cortex-associated f-actin and myosin. However, at the current state, the changes of upstream actomyosin signalling that lead to corresponding mechanical and structural changes of the cortex are not well understood. In this work, we show in breast epithelial cancer cells MCF-7 that EMT results in characteristic changes of the cortical signalling of Rho-GTPases Rac1, RhoA and RhoC and downstream actin regulators cofilin, mDia1 and Arp2/3. In the light of our findings, we propose that cell-cycle-dependent EMT-induced changes in cortical mechanics rely on two hitherto unknown signalling paths - i) a cell-cycle-dependent feedback between Rac1 and RhoC and ii) a negative feedback between Arp2/3 activity and cortical association of myosin II. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.30.526247v1?rss=1 Authors: Turlo, A. J., Hammond, D. E., Ramsbottom, K. A., Soul, J., Gillen, A., McDonald, K., Peffers, M. J., Clegg, P. D. Abstract: Variation in Mesenchymal Stromal Cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs is primarily attributed to secretion of various biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome composition remains largely unknown. Here, we examined the influence of donor age, sex and tissue source, on the protein profile of the equine MSC secretome. Initially, we used dynamic metabolic labelling with stable isotopes combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify secreted proteins in MSC conditioned media (CM). Seventy proteins were classified as classically-secreted based on the rate of isotope label incorporation into newly synthesised proteins released into the extracellular space. Next, we analysed CM of bone marrow- (n = 14) and adipose-derived MSCs (n = 16) with label-free LC-MS/MS proteomics. Clustering analysis of 314 proteins detected across all samples identified tissue source as the main factor driving variability in MSC CM proteomes. Linear modelling applied to the subset of 70 secreted proteins identified tissue-related difference in the abundance of 23 proteins. There was an age-related decrease in the abundance of two proteins (CTHRC1, LOX), which has been validated with western blot and enzymatic activity assay. There was limited evidence of sex-related differences in protein abundance. In conclusion, this study provides evidence that tissue source and donor age contribute to heterogeneity in the protein composition of MSC secretomes which may influence the effects of MSC-based cell therapy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.27.525849v1?rss=1 Authors: Riddell, J., Noureen, S. R., Sedda, L., Glover, J. D., Ho, W. K. W., Bain, C. A., Berbeglia, A., Brown, H., Anderson, C., Chen, Y., Crichton, M. L., Yates, C. A., Mort, R. L., Headon, D. J. Abstract: Embryonic mesenchymal cells are dispersed within an extracellular matrix but can coalesce to form condensates with key developmental roles. Cells within condensates undergo fate and morphological changes, and induce cell fate changes in nearby epithelia to produce structures including hair follicles, feathers or intestinal villi. Here, by imaging of mouse and chicken embryonic skin, we find that mesenchymal cells undergo much of their dispersal in early interphase, in a stereotyped process of displacement driven by three hours of rapid and persistent migration, followed by a long period of low motility. The cell division plane and the elevated migration speed and persistence of newly born mesenchymal cells are mechanosensitive, aligning with tension in the tissue. This early G1 migratory behaviour disperses mesenchymal cells and allows the daughters of recent divisions to travel long distances to enter dermal condensates, demonstrating an unanticipated effect of a cell cycle sub-phase on core mesenchymal behaviour. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Today Jonny is joined by the Founder of Dream Body Clinic, Joshua Ketner. Through his clinic, Josh works towards his goal of providing people from around the world access to medications and treatments that are difficult or impossible to get in their country of residence.They discuss:1. His catalyst to start his journey2. Mesenchymal stem cells and where they come from3. Real estate opportunities in MexicoJoshua Ketner, Founder and CEO of Dreambody Clinic, and his wife Venus Ketner, CFO, are set to release a new book that will provide readers with a comprehensive understanding of stem cell therapy and its benefits.Learn more about Joshua:Website: https://dreambody.clinic/Connect with Jonny!Cattani Capital Group: https://cattanicapitalgroup.com/Invest with us: invest@cattanicapitalgroup.comLinkedIn: https://www.linkedin.com/in/jonathan-cattani-53159b179/Jonny's Instagram: https://www.instagram.com/jonnycattani/IRR Podcast Instagram: https://www.instagram.com/theirrpodcast/TikTok: https://www.tiktok.com/@jonnycattaniYouTube: https://www.youtube.com/channel/UCljEz4pq_paQ9keABhJzt0AFacebook: https://www.facebook.com/jonathan.cattani.1

In this episode of the IJGC podcast, Editor-in-Chief, Dr. Pedro Ramirez, is joined by Dr. Elvio Silva to discuss precursors of ovarian cancer. Dr. Silva received a medical degree from the Universidad de La Plata and has been a faculty member at M.D. Anderson Cancer Center since 1980. He had pathology residences in Buenos Aires, Argentina, and University of Toronto, Canada and is the former President of the International Society of Gynecological Pathologists. Highlights: - Most ovarian serous tumors originate in the ovarian stroma. - Ovarian serous tumors originate in the epithelium of inclusion cysts or in epithelial areas that appear in the stroma due to mesenchymal-epithelial transition. - Mesenchymal-epithelial transition in serous tumors mimics the development of the Mullerian duct from the celomic mesenchyma.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.12.523351v1?rss=1 Authors: Feng, R., Tong, C., Lin, T., Liu, H., Shao, C., Li, Y., Sticht, C., Kan, K., Li, X., Liu, R., Wang, S., Wang, S., Munker, S., Niess, H., Meyer, C., Liebe, R., Ebert, M. P., Dooley, S., Wang, H., Ding, H., Weng, H.-L. Abstract: To date, epithelial-to-mesenchymal transition (EMT) has been observed in cultured hepatocytes, but not in vivo. TGF-beta is supposed to initiate EMT in hepatocytes by inhibiting the hepatic master transcription factor HNF4alpha through the SMAD2/3 complex. However, we observe that the SMAD2/3 complex is required for HNF4alpha transcription. Besides SMAD2/3, C/EBPalpha is also essential for constitutive HNF4alpha expression in hepatocytes. In contrast to upregulating HNF4alpha transcription, SMAD2/3 represses C/EBPalpha transcription. Therefore, long-term TGF-beta incubation results in C/EBPalpha depletion, which inhibits HNF4alpha expression. Impressively, SMAD2/3 binding to the CEBPA promoter is inhibited by insulin. Maintaining a high insulin concentration in culture medium completely inhibits TGF-beta-induced hepatocyte EMT. Insulin inhibits TGF-beta-induced SMAD2/3 binding to the promoters of core EMT transcription factors e.g., SNAI1. SNAI1 transcription requires both SMAD2/3 and FOXO1 in nuclei. Insulin inhibits SNAI1 transcription through impeding SMAD2/3 binding to its promoter and inducing FOXO1 phosphorylation. Hence, insulin is the key factor that prevents TGF-beta-induced EMT in hepatocytes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.31.522383v1?rss=1 Authors: Matsubayashi, H. T., Mountain, J., Yao, T., Peterson, A. F., Deb Roy, A., Inoue, T. Abstract: Class IA phosphoinositide 3-kinase (PI3K) galvanizes fundamental cellular processes such as migration, proliferation, and differentiation. To enable multifaceted roles, the catalytic subunit p110 utilizes a multi-domain, regulatory subunit p85 through its inter SH2 domain (iSH2). In cell migration, their product PI(3,4,5)P3 generates locomotive activity. While non-catalytic roles are also implicated, underlying mechanisms and its relationship to PI(3,4,5)P3 signaling remain elusive. Here, we report that a disordered region of iSH2 contains previously uncharacterized AP-2 binding motifs which can trigger clathrin and dynamin-mediated endocytosis independent of PI3K catalytic activity. The AP-2 binding motif mutants of p85 aberrantly accumulate at focal adhesions and upregulate both velocity and persistency in fibroblast migration. We thus propose the dual functionality of PI3K in the control of cell motility, catalytic and non-catalytic, arising distinctly from juxtaposed regions within iSH2. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.16.520731v1?rss=1 Authors: Bartlome, S., Xiao, Y., Ross, E., Dalby, M. J., Berry, C. C. Abstract: Breast cancer is the leading cause of cancer mortality in women worldwide and commonly metastasizes to the bone marrow, drastically reducing patient prognosis and survival. In the bone marrow niche, metastatic cells can enter into a dormant state, thereby evading immune surveillance and treatment, and can be reactivated to enter a proliferative state due to poorly understood cues. Mesenchymal stromal cells (MSCs) maintain cells in this niche partly by secreting extracellular matrix and paracrine factors and by responding to regenerative cues. MSCs also produce extracellular vesicles (EVs) that carry a range of cargoes, some of which are implicated in cell signalling. Here, we investigate if the changing metabolic state of MSCs alters the cargoes they package into EVs, and how these changing cargoes act on dormant breast cancer cells (BCCs) using an in vitro BCC spheroid model and a scratch assay to create a regenerative demand on MSCs. Our findings show that EVs produced by standard MSCs contain glycolytic metabolites that maintain BCC dormancy. When MSCs are placed under a regenerative demand and increase their respiration to fuel differentiation, these metabolites disappear from the EV cargo and their absence encourages rapid growth in the BCC spheroids. This work implicates EVs in cancer cell dormancy in the bone marrow niche and indicates that pressures on the niche, such as regeneration, can be a driver of BCC activation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.11.519940v1?rss=1 Authors: Theret, M., Messing, M., White, Z., Henry, L. W., Rempel, L., Hamer, M., Hashimoto, J., Li, F. F., Brassard, J., Li, Y., Sauge, E., Shin, S., Day, K., Uppal, M., Low, M., Eisner, C., Sato, S., Akira, S., Bernatchez, P., McNagny, K., Rossi, F. M. V. Abstract: The ability of mesenchymal stromal cells to modulate inflammation is at the basis of the ongoing interest in their therapeutic potential. Yet, reliable success in clinical trials is limited, possibly due to a limited understanding of their impact on the inflammatory milieu in physiological conditions. Here we show that, at steady state, mesenchymal progenitors regulate the balance between type 1 and type 2 inflammatory milieus by acting on innate immune cells through the TAK1-NFkB pathway. Suppressing the constitutive activity of this pathway in MPs leads to skewing of the immune system toward systemic Type 2 inflammation (Th2). These changes have significant effects on diseases with an important inflammatory component, leading to a worsening of disease in a preclinical model of Th2-dependent Asthma, and a reduction of symptoms associated with Th1/Th17-dependent experimental autoimmune encephalitis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Respir Res. 2017 Sep 6;18(1):168 Front Behav Neurosci. 2020; 14: 24 JLR Methods| 2020.Volume 61, ISSUE 11, P1512-1523, November 01 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.25.517972v1?rss=1 Authors: Maurizi, E., Merra, A., Macaluso, C., Schiroli, D., Pellegrini, G. Abstract: Human corneal endothelial cells are organized in a tight mosaic of hexagonal cells and serve a critical function in maintaining corneal hydration and clear vision. Regeneration of the corneal endothelial tissue is hampered by its poor proliferative capacity, which is partially retrieved in vitro, albeit only for a limited number of passages before the cells undergo mesenchymal transition (EnMT). Although different culture conditions have been proposed in order to delay this process and prolong the number of cell passages, EnMT has still not been fully understood and successfully counteracted. In this perspective, we identified herein a single GSK3 inhibitor, CHIR99021, able to revert and avoid EnMT in primary human corneal endothelial cells (HCEnCs) from old donors until late passages in vitro (P8), as shown from cell morphology analysis (circularity). In accordance, CHIR99021 reduced expression of alpha-SMA, an EnMT marker, while restored endothelial markers such as ZO-1, Na+/K+ ATPase and N-cadherin, without increasing cell proliferation. A further analysis on RNA expression confirmed CHIR99021 induced downregulation of EnMT markers (alpha-SMA and CD44), upregulation of the proliferation repressor p21 and revealed novel insights into the beta-catenin and TGFbeta; pathways intersections in HCEnCs. The use of CHIR99021 sheds light on the mechanisms involved in EnMT and brings a substantial advantage in maintaining primary HCEnCs in culture until late passages, while preserving the correct morphology and phenotype. Altogether, these results bring crucial advancements towards the improvement of the corneal endothelial cells based therapy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Steven Samson is an internationally recognized pioneer in orthopedic regenerative medicine. He founded the Orthohealing Center, a premier medical clinic in Los Angeles, California, specializing in non-surgical orthopedic and cell-based medicine.  Recently, Dr. Samson created Bio-recovery labs, utilizing machine-based energy including shock waves to stimulate the body's natural healing capacity. Autology is a specialty in the use of stem cells to stimulate natural healing.  What are Stem Cells? The term "stem cell" has been thrown around a lot in recent years, and it's important to understand what it actually means.  Stem cells are cells that have the ability to self-renew and differentiate into other cell types. In other words, they have the ability to repair and regenerate damaged tissue. There are different types of stem cells, including: Embryonic stem cells, which are derived from embryos And adult stem cells, which are found in adults.  There are also induced pluripotent stem cells, which are created from adult cells that have been genetically reprogrammed to act like embryonic stem cells. The most common type of stem cell therapy is autologous stem cell therapy, which uses your own stem cells.  This can be done by harvesting bone marrow from your hip or fat from your abdomen, and injecting it into the damaged area.  This type of therapy is still considered experimental, but there is some evidence that it can be effective in treating conditions. The difference between orthopedic and cell-based medicine Orthopedic medicine is the branch of medicine that deals with the diagnosis and treatment of disorders of the musculoskeletal system.  Orthopedic surgeons use a variety of techniques to treat these conditions, including surgery, medication, physical therapy, and lifestyle changes. Cell-based medicine is a relatively new field that uses a patient's own cells to treat various conditions.  This type of treatment is often used in regenerative medicine, which aims to repair or replace damaged tissue.  Cell-based therapies are also being used to treat cancer and other diseases. Regenerative Medicine Regenerative medicine is a branch of medicine that focuses on the regeneration of tissues and organs.  This can be done through the use of stem cells, growth factors, and other cell-based therapies.  Regenerative medicine has the potential to treat a wide variety of conditions, including injuries, degenerative diseases, and congenital defects. One of the major benefits of regenerative medicine is that it has the potential to heal tissues and organs without surgery or drugs.  This can lead to fewer side effects and faster recovery times for patients.  Additionally, regenerative therapies can be customized to each individual patient, which means that the treatments are more likely to be effective. In this Podcast you'll learn about: Regenerative medicine Autology Prp (platelet-rich plasma) Mesenchymal stem cells Shockwave therapy  And so much more. EPISODE RESOURCES: www.tobiconference.com www.orthohealing.com www.drstevensampson.com www.biorecoverylabs.com

In this episode, Per-Ola Carlsson joins us to discuss Mesenchymal stromal cells to intervene in the development of type 1 diabetes. Ask the Expert is a ~30 minute digital cafe experience where scientists and grad students can meet and exchange with thought leaders in the field of type 1 diabetes. Link below to sign up for a seat in the cafe!

Stem Cell Treatments actually help to replace damaged cells so you will heal quickly after a orthopedic surgery also help to relieve symptoms of pain. Mesenchymal stem cells are the most effective in orthopedic treatments. These stem cells possess a potent ability to repair musculoskeletal tissue such as cartilage and bone.

Duane Peters from the Lupus Foundation of America interviews Dr Gary Gilkeson from the Medical University of South Carolina about a phase I trial into the use of mesenchymal stromal cells (MSC) in refractory lupus patients in the USA, following impressive results of clinical improvement resulting from this therapy in China. The trial indicated that infusions of MSCs derived from the umbilical cord are safe and may be effective in treating mild to moderate systemic lupus erythematosus, with minimal adverse effects. Access the article: http://dx.doi.org/10.1136/lupus-2022-000704

Stem Cells For Autoimmune Diseases Autoimmune diseases encompass a vast array of disorders in which an overactive immune system attacks its own cells and tissues leading to devastating consequences. In other words, your body damages and fights against itself. Researchers have identified greater than 100 different autoimmune diseases which are often chronic, debilitating and life threatening. Besides healing damaged tissues, stem cells have the unique ability to influence the immune system, shutting off pathological responses while preserving its ability to fight off disease. Stem cells and specifically, mesenchymal stem cells target and are attracted to inflamed tissue and start producing anti-inflammatory agents. Mesenchymal stem cells have the potential to induce the production of T regulatory cells, a type of immune cell whose function is to protect the body against immunological self-attack.

Medicine should improve people's health. Yet, Western medicine focuses on symptoms, often disregarding how our bodies function as a system. Over the years, there is an emerging trend of leveraging functional medicine to tackle this very problem by using a more holistic approach. Did you know that the approach of functional medicine is not new? In fact, Chinese medicine works similarly. Functional medicine is not only about integrating these two medicinal disciplines, but it's also creating a new standard for healthcare. Stem cell therapy is found to be effective for so many conditions, from autoimmune diseases to neurological problems. With increasing research on the treatment, stem cell therapy continues to show potential positive results for more health conditions. It also has powerful anti-ageing properties.    In this episode, stem cell therapy pioneer Dr Joy Kong joins us to share her experience in the medical industry and why she focused on stem cell therapy. She shares its numerous benefits and how people can use it based on their conditions. Our health functions as an overall system. It's no longer enough to depend on the Western approach of treating symptoms — we need to get to the root problems.   If you want to learn more about fighting ageing and diseases through stem cell therapy, then this episode is for you! Here are three reasons why you should listen to the full episode: Discover what stem cell therapy is and how it can treat various conditions.  Understand the importance of treating root problems rather than symptoms.  Learn how to leverage stem cell therapy depending on your goals. Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to https://www.peakwellness.co.nz/epigenetics. Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer  Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5-km or run a 100-miler? ​​Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle?  Go to www.runninghotcoaching.com for our online run training coaching. Health Optimisation and Life Coaching Are you struggling with a health issue and need people who look outside the square and are connected to some of the greatest science and health minds in the world? Then reach out to us at support@lisatamati.com. We can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity or want to take your performance to the next level and want to learn how to increase your mental toughness, emotional resilience, foundational health, and more, contact us at support@lisatamati.com. Order My Books My latest book Relentless chronicles the inspiring journey about how my mother and I defied the odds after an aneurysm left my mum Isobel with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions all around the world, go to https://shop.lisatamati.com/collections/books. Lisa's Anti-Ageing and Longevity Supplements  NMN: Nicotinamide Mononucleotide, an NAD+ precursor Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health so you can live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and rigorously tested by an independent, third-party lab. Start your cellular rejuvenation journey today. Support Your Healthy Ageing We offer powerful third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. 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The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Ketone Products by Keto-Pro Exogenous Ketones developed by Nutritionist and Body Building champion Richard Smith. Keto-Pro BHB Exogenous Ketones –  250g   MORE BHB per gram than other MARKET LEADERS. During In-house testing, Keto-Pro BHB raised ketones quicker, higher and for longer than other market leaders. Grab your Ketones here. My ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection. Resources Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron! Are All MSCs Created Equal? from Dr Joy Kong American Academy of Integrative Cell Therapy THEA Center for Regenerative Medicine Tiger of Beijing: The Inspirational Memoir of a Fierce Regenerative Medicine Physician by Dr Joy Kong The Web That Has No Weaver: Understanding Chinese Medicine by Ted Kaptchuk Connect with Dr Joy: Uplyft Center | Chara Biologics | LinkedIn | Facebook | Instagram | YouTube Episode Highlights [02:53] Dr Joy's Background Dr Joy moved from China to the US at 20 years old. She wrote a book detailing her 3-year journey of getting into the US and adapting to the culture. Growing up in a Chinese family, Dr Joy was used to both Western and Chinese medicine. Chinese medicine looks at the human body as a system and complex web. This is what Western medicine lacks. When trying to integrate Chinese and Western medicine together, Dr Joy ran into the problem of different languages. Then, she discovered the emerging field of functional and anti-ageing medicine, which also treats the body as a system. [09:44] Healthcare as We Know It Needs to Change Despite having the biggest spending per capita on healthcare, America remains rampant with obesity and chronic diseases.  Over time, people began accepting Chinese medicine practices like acupuncture.  It's the same thing with stem cell therapy. Its benefits are now more widely understood. [13:51] What Is Stem Cell Therapy?  All our tissues contain stem cells, and it's only until they form organs that they create specialised cells. The gold standard used in stem cell therapy is mesenchymal stem cells because of its more general function. Mesenchymal stem cells modulate the environment they're in. Listen to the full episode to hear Dr Joy's explanation of how these stem cells create a coordinating effect. Stem cell therapy can produce incredible results and transform people's lives. [20:42] Are All Mesenchymal Stem Cells Equal? Dr Joy uses birth tissue-derived stem cells from healthy births.  In her research, she found that birth tissue-derived stem cells are better than those derived from bone marrow and fat.   Birth tissue-derived stem cells are more potent because they're primitive, active, have more anti-inflammatory capabilities, and can shift your immune system.  All embryonic and adult stem cells have the potential to cause tumour formation and promote existing cancer.  However, birth tissue-derived stem cells don't have this potential and can also detect cancer. [28:17] How to Use Stem Cell Therapy Utilising stem cell therapy depends on your goals. For example, if you're an athlete who injured your ligaments or tendon, the therapy involves a direct injection on the injury. Older adults with chronic inflammatory conditions will need a systemic approach to regenerate the whole body. Dr Joy uses both IV injections and direct injections to the knee for patients with osteoarthritis. The therapy is so potent that it can help change the internal environment of your body. Inflammation can actually make stem cells work better. You don't need to wait to get your inflammation levels down before getting the therapy. [35:09] Benefits of Stem Cell Therapy Dr Joy observed that stem cell therapy can help people with various kinds of systemic conditions.  Even if you inject the stem cells in one area, they will eventually get into the bloodstream and become systemic.  For patients with a significant illness, Dr Joy recommends getting at least 2-3 sessions. Meanwhile, Dr Joy recommends a session every 3-6 months to address anti-ageing concerns. [38:53] Getting to Where She Is Dr Joy got into medicine because she wanted to make a difference in people's lives. She worked in psychiatry before, and while the medicine helped patients, they did not address root causes. Stem cells are currently the most holistic treatment available. It's not injecting molecules — it's injecting intelligence. She loves learning different disciplines, and she realised how all the organs have common themes. [43:11] Functional Medicine Will Become the Standard  Functional medicine will someday become the standard approach in medicine because it addresses root causes and not just symptoms. It's a grassroots movement because it's people and patients who will advocate for it, rather than doctors.  More people are realising that conventional medicine is no longer enough. [45:40] Emerging Research in Stem Cell Therapy  There's now more research on stem cell therapy. Currently, most of it focuses on autoimmune diseases.  There's also research on diabetes, neurological conditions, stroke, injuries, inflammatory diseases, autism, and addiction, among others. In addition, it can increase lifespan by about 30% and regenerate your brain, eyes, and more. Listen to the full episode to hear more about stem cell research! [50:38] What Happens as We Age?  We run out of stem cells as we age because of inflammation. We also keep using them throughout life. Thus, it's not recommended to keep activating your own stem cells.  When we're born, one in 10,000 cells is a mesenchymal stem cell. By our 40s, this drops to one in 400,000, then one in 2 million by our 80s.  Stem cells are the engine for regeneration. Stem cell therapy is becoming more accessible worldwide. [54:41] Should We Bank Our Children's Cells?  Dr Joy shares that it is useful to bank your own child's cells. But using other people's cells is also okay.  When we put stem cells into our bodies, they will be activated and eventually die off.  If you're trying to bank your child's cells for your own use, the tissue bank may not release it for you.  Stem cell therapy is going to advance so that you probably don't even need to bank your child's cells. 7 Powerful Quotes ‘There's no prejudice. It just all about, “Okay, for this, this Chinese medicine work much better. And for this problem, okay, let's do this Western medicine. That works much better than the Chinese medicine.”' ‘The Western medicine doesn't yet have a system to understand how you put all these relationships together. That's where it's lacking. And that's where I wanted to borrow some of the wisdom from Eastern medicine, where you can look at the body from a system point of view.' ‘I think hope is really important. There's so many conditions where traditional doctors just said, “There's no more we can do.” And then they come to do stem cells, and they get incredible results. So we are transforming people's lives.' ‘The younger stem cells from birth tissue have much better capability of detecting that cancer, so it can tell the cancer to die.' ‘There has been evidence that high inflammation actually make the stem cell work better. Basically, the inflammation of the body sends signals, so they make the cells more active. It's a double edged sword.' ‘No, I'm not the boss. I'm just really driven and really want to understand. I think it's intellectual curiosity and it's passion because I went into medicine to really make a difference for people's lives.' ‘I call stem cells the engine for regeneration, and everything else we're doing, like the hyperbaric, like the nutritional therapy, light therapy, all these things are the fuel. Eventually, it fills the body, but it also fills the engine. The engine needs all these important factors, but you still need the engine. If you don't have that engine, you're not going anywhere.' About Dr Joy Dr Joy Kong is a triple-board certified physician for the American Board of Psychiatry and Neurology, American Board of Addiction Medicine, and American Board of Anti-aging and Regenerative Medicine. She founded Chara Biologics to provide the best regenerative medicine in the country. She also founded the American Academy of Integrative Cell Therapy to provide physician education and training in regenerative medicine. Joy is also the founder and medical director of Uplyft Longevity Center, which aims to use cutting-edge therapies to help people suffering from chronic and degenerative conditions, as well as optimise people's health.  Joy embraces practising medicine in a holistic, comprehensive, and personalised manner by treating the root causes of illnesses, not just the symptoms. She is passionate about regenerative medicine and has lectured internationally on stem cell treatment and has worked with various cell laboratories in the US.  Joy also wrote her memoir, Tiger of Beijing, detailing her 3-year journey of coming to the United States at the age of 20. The book won the 2020 Book of the Year by IAOTP.  Want to learn more about stem cell therapy and regenerative medicine? Check out Uplyft Center and Chara Biologics.  You can also connect with Joy on LinkedIn, Facebook, Instagram, and YouTube. Enjoyed This Podcast? If you did, be sure to subscribe and share it with your friends! Post a review and share it! If you enjoyed tuning in, then leave us a review. You can also share this with your family and friends so they can know how to optimise sleep.  Have any questions? You can contact me through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa  

Welcome to another episode of the Dr. Lo Radio Show! I really enjoyed recording this episode, and I think you will enjoy it as well. Today I am chatting with Dr. Joy Kong and we are talking all about stem cell therapy and regenerative medicine. Dr. Kong is a triple board-certified by American Board of Psychiatry & Neurology, American Board of Addiction Medicine, and American Board Anti-Aging & Regenerative Medicine. After graduating as a valedictorian from San Francisco State University, Dr. Kong completed her medical training at UCLA School of Medicine. As the result of her intense interest in the human brain, she specialized in psychiatry, and worked at a Veterans Affairs hospital and LA county hospital. While working in the hospital ER and in county clinics, she realized the futility of trying to treat someone without examining the person in a holistic manner, which led to her interest in integrative medicine. She became very passionate about regenerative medicine because of the transformative power it brings, and the sound science it is based on. She is keen on keeping up with the latest scientific discoveries and technology, and consulted with many regenerative medicine experts from around the world, and has lectured internationally. Dr. Kong is dedicated to educating other physicians on the principles and implementation of regenerative medicine, so a great many more people can be helped. We talk about so many great things in this episode. We talk about the hierarchy of stem cells. We talk about stem cell therapy's immune, angiogenic, anti-microbial, anti-inflammatory, regenerative beneficial effects. And we talk about looking at the body as a complex, interconnected, webbed system. If you are listening to this episode and you or someone you know is navigating through any of the health issues we discuss, I would be more than happy to support you in the journey! I work with people virtually and in-person in San Diego. Feel free to reach out to me to continue this conversation: @doctor_lo I hope you enjoy and learn something new from this episode! We Discuss: {07:03} Introducing Dr. Joy Kong {10:57} The linear view of diseases and why it is not favored {11:40} The body as a web or a system {14:42} Mesenchymal stem cells {16:02} The programmed cell death {17:07} The discouraged practice of using fetal stem cells {19:42} The mesenchymal stem cells for anti-inflamatory action {22:28} Mesenchymal stem cells can help with autoimmune diseases {24:12} The success cases of using mesenchymal stem cells {26:46} The positive encounter with the brother of a radio show host {30:47} The umbilical cord tissue is rich in mesenchymal stem cells which can be used in cancer treatment {31:54} The cost of stem cell treatment And so much more! Links Mentioned: Guest Website https://www.uplyftcenter.com Guest on Instagram https://www.instagram.com/dr_joy_kong/ Shine Natural Medicine https://shinenaturalmedicine.com/ Paleovalley https://paleovalley.com/ 15% off with CODE: DRLO

As you age, you lose stem cells. Scientists have found that collecting younger samples of these cells can be effective for future medical treatment. Being your own stem cell donor can come with a plethora of benefits, and many researchers believe that you will thank yourself later for thinking ahead.  Joining us on this podcast is Steven Clausnitzer. Steven is the CEO and co-founder of Forever Labs, an adult stem cell banking and storage company. Forever Labs uses an outpatient procedure to harvest adult Mesenchymal stem cells for prospective medical treatments down the road.  In this episode, you will hear Steven address topics such as: The origins of Forever Labs. The advantages of stem cell banking and storage.  The procedures behind stem cell harvesting.  How using stem cells prophylactically can prevent age-related diseases.   Offer: This episode is sponsored by Bowmar Nutrition. To receive a 5% discount, use the code GENIUS5 at checkout. Go to BowmarNutrition.com to shop now! To learn more about Forever Labs and their services, you can visit foreverlabs.com.  

In this week's episode, we'll talk about the functional properties of mesenchymal stromal cells in sickle cell disease, learn more about CAR T-cell-mediated hematotoxicity in relapsed/refractory B-cell lymphoma, and discuss dual cytokine blockade in graft-versus-host disease.

The host is joined by Dr. Andres Acosta from the Brigham and Women Hospital. Dr Acosta discusses, on behalf of a distinguished group of coauthors, their recent somewhat provocative modern pathology publication proposing that mesenchymal neoplasms of the prostate are morphologically and molecularly heterogeneous lesions that include neoplasms that harbor genetic aberrations seen in specific mesenchymal tumors arising in other anatomic sites, such as soft tissue and the uterus. Study by Acosta et al, Re-evaluating tumors of purported specialized prostatic stromal origin reveals molecular heterogeneity, including non-recurring gene fusions characteristic of uterine and soft tissue sarcoma subtypes. Modern Pathology, 34, 1763–1779 (2021). https://www.nature.com/articles/s41379-021-00818-6. See acast.com/privacy for privacy and opt-out information.

Chromatin instability leads to alterations in gene expression that re-directs cellular senescence by corruption of chemokine and cytokine signalling resulting in epithelial to mesenchymal transitions and the potential for metastatic cancer in the elderly . As lymphocyte lineage's age these underlying pathobiochemical events are potentiated by hypo and hyper immune responses thus generating a downward reductio to misdirected hyperinflammatory states and the potential for autoimmune disease sequalae. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Oncotarget published "Carcinoma cells that have undergone an epithelial-mesenchymal transition differentiate into endothelial cells and contribute to tumor growth" which reported that the authors investigated whether EMT can confer endothelial attributes upon carcinoma cells, augmenting tumor growth and vascularization. Hypoxic regions, demarcated by HIF-1α staining, exhibited focal areas of E-cadherin loss and elevated levels of vimentin and the EMT-mediator FOXC2. Implantation of MCF-7 cells, co-mixed with human mammary epithelial cells overexpressing the EMT-inducer Snail, markedly potentiated tumor growth and vascularization, compared with MCF-7 cells injected alone or co-mixed with HMLE-vector cells. Intra-tumoral vessels contained CD31-positive cells derived from either donor cell type. FOXC2 knockdown abrogated the potentiating effects of HMLE-Snail cells on MCF-7 tumor growth and vascularization, and compromised endothelial transdifferentiation of mesenchymal cells cultured in endothelial growth medium. Hence, cells that have undergone EMT can promote tumor growth and neovascularization either indirectly, by promoting endothelial transdifferentiation of carcinoma cells, or directly, by acquiring an endothelial phenotype, with FOXC2 playing key roles in these processes. A fourth mechanism—termed vasculogenic mimicry—entails the de novo generation of microvessels, lined with highly invasive tumor cells embedded in a rich extracellular matrix, essentially mimicking a true vascular endothelium and, notably, lacking in the endothelial cell markers CD31 and CD34. Finally, newly formed blood vessels may emerge through transdifferentiation of neoplastic or tumor stem-like cells into CD31-positive endothelial-like cells, as has been documented in neuroblastoma, B-cell lymphoma, and glioblastoma. In addition, subcutaneous injection of B16 melanoma cells into Foxc2 haploinsufficient mice has been shown to lead to the impaired formation of tumor blood vessels and, accordingly, compromise tumor growth. Given the inherent plasticity of cells that have undergone EMT and the involvement of hypoxia in EMT and angiogenesis, the authors sought to ascertain whether cells, undergoing EMT in the hypoxic milieu, can acquire endothelial cell attributes and augment tumor growth by directly contributing to the tumor vasculature. These findings findings link the stemness, conferred through EMT, to the acquisition of endothelial cell traits and the augmentation of tumor angiogenesis in a FOXC2-dependent manner. The Sarkar Research Team concluded in their Oncotarget Research Output that their findings are consistent with the notion that the phenotypic attributes of cells within growing tumors are eminently pliable and that, as tumor size and the oxygen deficit increase, carcinoma cells become progressively dedifferentiated towards a mesenchymal, stem-like phenotype. DOI - https://doi.org/10.18632/oncotarget.27940

Trends in Immunology Volume 36, Issue 4, 2015, 217–228 Carcinogenesis 2015;36:1180-1192 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Clinical and Molecular Allergy volume 15, Article number: 21 (2017) Front. Immunol., 25 September 2019 | https://doi.org/10.3389/fimmu.2019.02247 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

•Impaired immunological responsiveness is common in the elderly •The immunological competence of an individual is determined by the presence of mature lymphocytes formed in primary lymphoid organs, and secondary lymphoid tissues such as the liver, lung and GI tract. •Immunological equilibrium requires steady lymphocyte output, and controlled expansion •Thymic and lymph-node stromal microenvironments thus represent key elements in the development of the adaptive immune system. Consequently, impairment of the lymphoid microenvironment will ultimately lead to insufficient primary and secondary immune responses or to the decline of thymic selection, manifesting in immune senescence accompanied by late-onset autoimmune disorders, often observed in elderly. •Self-tolerant cytotoxic and helper T-lymphocytes, the crucial regulator cells in adaptive immune responses, develop in the specialized epithelial network of the thymus. The thymus, however, gradually loses its capacity to support lymphopoiesis in an involution process that results in a decline of de novo T-cell production. •Cancers of epithelial origin (carcinomas) are the most frequent type of malignancy in humans, with their incidence and aggressiveness increasing with age •This observation raises the question as to whether the aging process itself contributes to tumor progression •. In this regard, telomere biology seems to play a pivotal role since shortening of telomeres has been associated with cellular senescence and organismal aging as well as with cancer incidence and mortality . • •In the multistep carcinogenesis model, telomere shortening has been observed together with increased chromosome instability (CIN) in early precancerous conditions •Experimental models have also shown that a transient period of telomere instability followed by reactivation of telomerase contributes to the acquisition of the metastatic phenotype --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

In Part 2, Dr. Matthay provides the rationale behind treating ARDS patients with MSC. Initial studies in a mouse model of ARDS, showed that treatment with MSCs increased levels of anti-inflammatory cytokines and antimicrobial peptides in the lung, and increased phagocytosis of bacteria by monocytes. Further studies in ex vivo perfused human lungs and in sheep with severe lung injury showed that treatment with MSCs improved oxygenation and reduced pulmonary edema. An NIH/NHLBI supported phase 1 clinical trial for safety has been completed and a randomized, blinded phase 2 trial has now been initiated to test the safety and efficacy of MSC treatment in human patients with ARDS.

Acute respiratory distress syndrome is a life threatening condition with few effective treatment options. Preliminary studies using mesenchymal stem cells, or stromal cells, to treat ARDS have shown promise with decreased levels of bacteria in the lungs, reduced pulmonary edema and improved oxygenation. In Part 1, Dr. Calfee begins by explaining that acute respiratory distress syndrome (ARDS) is pulmonary edema, or fluid in the lungs, not due to heart failure. It is a condition that affects 200,000 people/year in the USA with a 30-40% mortality rate. During ARDS, there are many cellular changes with complex pathophysiology making it extremely difficult to treat. Currently, patients are treated by ventilation with low tidal volume and fluid conservative therapy as many pharmacological interventions have failed. Mesenchymal stem cells (MSC), however, may hold promise as a treatment.

You’ve probably heard of exosomes by now but with so many information out there, it can be difficult to filter out information about what they can and can’t do. So on this new episode of the Regenerative Warrior podcast, I sat down with Dr. Ed Park to talk about what exosomes are, what they can do and more importantly, what kind of exosomes are best for you or your practice. We also talked about the following topics: - Mesenchymal exosomes and how they guide regeneration - What is the difference between exosomes and viruses - Some benefits of exosomes use Stay tuned!

Commentary by Dr. Ileana L. Piña

Featuring: Mark M. Mikhael, MD; Deepak Reddy, MD; Bradley Saitta, MD; Nick Shamie, MD Disclosures: Mikhael, Mark M.: Consulting: Clariance Spine (B), GS Medical (B). Reddy, Deepak: Nothing to Disclose. Saitta, Bradley: Nothing to Disclose. Shamie, Nick: Royalties: Seaspine (B); Stock Ownership: SI Bone (100000 Shares, 1%), Vertiflex (200000 Shares, 1%); Consulting: Stryker (Financial, 0), Seaspine (Financial, 0), SI Bone (Financial, 0), Vertiflex (Financial, 0); Speaking and/or Teaching Arrangements: Medtronic (Financial, 0); Trips/Travel: Medtronic (Financial, 0); Board of Directors: Vertiflex (Financial, Medical Director); Scientific Advisory Board: SI Bone (Financial, Medical Advisory Board). Key: A: $100-$1,000; B: $1001-$10,000; C: $10,001-$25,000; D: $25,001-$50,000; E: $50,001-$100,000; F: $100,001- $500,000; G: $500,001-$1M; H: $1,000,001- $2.5M; I: $2.5M+

Dr. Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.                                                 Our feature discussion this week centers on the temporal changes in natriuretic peptides preceding heart failure hospitalizations and patients at high risk. Data that are really novel and have implications for the way we perhaps monitor and categorize these high risk patients. Well, more soon right after these summaries.                                                 The first original paper this week provides the first epigenome-wide association study in patients with heart failure. Now, epigenetics refers to biochemical DNA modification such as methylation of gene bodies, and post-translational modification of histones, which is increasingly recognized to play a crucial, regulatory interface between genes, environment, and the transcriptome.                                                 The lack of availability of myocardial specimens from patients has been a major roadblock for elucidating the impact of such epigenetic changes on complex cardiovascular traits. However, in today's paper from first author, Dr. Meder, corresponding author, Dr. Katiz and colleagues from University of Heidelberg, Germany. The authors performed the first multi-omic study in myocardial tissue and blood of patients with dilated cardiomyopathy compared to controls.                                                 They detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy, with three of them reaching epigenome-wide significance. 29 of these loci could be replicated in independent cohorts and authors further linked a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression.                                                 Finally, they identified distinct epigenetic methylation patterns that are conserved across tissues. Thus representing novel, epigenetic biomarkers for heart failure.                                                 The next study is the first to assess a diagnostic and prognostic value of cardiac myosin binding protein-C in patients presented with possible acute myocardial infarction or AMI. Cardiac myosin binding protein-C is a cardiac restricted protein that is more abundant than the cardiac troponins and is released more rapidly following AMI.                                                 In today's paper, first author, Dr. Kaya, corresponding author, Dr. Marber and colleagues from the Rayne Institute In St. Thomas's hospital in London evaluated cardiac myosin binding protein-C as an adjunct or alternative to cardiac troponins in the early diagnosis of AMI in 1,954 unselected patients presenting to the emergency department with symptoms suggestive of AMI.                                                 The final diagnosis of AMI was independently adjudicated in 340 patients. The authors found that concentrations of cardiac myosin binding protein-C at presentation were significantly higher in those with versus without an AMI. The discriminatory power for AMI quantified by the area under receiver operating curve was comparable for cardiac myosin binding protein-C to high sensitivity cardiac troponins T and I, and even superior to standard sensitivity cardiac troponin I. The use of cardiac myosin binding protein-C more accurately classified patients with a single blood test and to rule out or rule in categories in early presenters, meaning those with chest pain of less than three hours.                                                 The improvement in rule in or rule out classification with cardiac myosin binding protein-C was larger compared with higher sensitivity cardiac troponins T and I. Finally, cardiac myosin binding protein-C was superior to high sensitivity and standard troponin I and similar to high sensitivity cardiac troponin T at predicting death at three years. Thus in summary, this paper shows that cardiac myosin binding protein-C at presentation provides discriminatory power comparable to high sensitivity troponins T and I in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset.                                                 The next paper describes the discovery of a novel candidate cardiomyopathy or arrhythmia gene. First author, Dr. Barryfield, corresponding author Dr. McNally from Center of Genetic Medicine in Chicago and colleagues studied a family with dilated cardiomyopathy and associated conducted system disease in whom prior clinical cardiac gene panel testing was unrevealing. Whole genome sequencing however, identified a premature stop codon in the gene encoding a novel myo filament component, the myosin binding protein-H-like.                                                 Having identified this gene, they turned to experimental approaches. The myosin binding protein-H-like gene was found to have high atrial expression with low ventricular expression. The truncated protein failed to incorporate into the myo filament. Human cell modeling demonstrated reduced expression of the mutant allele. Heterozygotes and nullumites exhibited a reduction in fractional shortening and increased diastolic ventricular chamber size, aberrant atrio-ventricular conduction and an increased rate of arrhythmia associated with the expression of the myosin binding protein-H-like in the atria, as well as in discrete puncta throughout the right ventricular wall and septum.                                                 These findings therefore support that myosin binding protein-H-like truncations may increase the risk for human arrhythmias and cardiomyopathy.                                                 Transplantation of cells into the infarctant heart has significant potential to improve myocardial recovery. However, low efficacy of cell engraftments still limits the therapeutic benefit. In today's paper, authors describe a method for the unbiased, in-vivo selection of cytokines that may improve Mesenchymal stromal cell engraftment into the heart. In this paper from first author, Dr. Bortolotti, corresponding author Dr. Giacca, and colleagues from University of Trieste in Italy, an arrayed library of 80 secreted factors were individually cloned into adeno-associated viral vectors.                                                 Pools from this library were then used for the batch transduction of bone marrow derived Mesenchymal stromal cells ex-vivo, followed by intra myocardial cell administration in normal and infarctant mice. Three weeks after injection, the vector genomes were recovered from the few persisting cells, and identified by sequencing DNA barcodes that were uniquely labeled for each of the tested cytokines.                                                 Using this novel, competitive, engraftment screening methodology, the authors identified that the most effective molecule was cardiotrophin-1 a member of the IL-6 family. Intra cardiac injection of Mesenchymal stromal cells preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size parallel to the persistence of the transplanted cells in the healing hearts for at least two months after injection. Thus, preconditioning with cardiotrophin-1 might represent an efficient manner to improve the currently poor cell retention in patients treated with Mesenchymal stromal cell therapy.                                                 The final paper presents results of the early myo trial, a non-inferiority trial comparing a pharmacoinvasive strategy with half-dose alteplase versus primary PCI in patients with STEMI, presenting six hours or less after symptom onset but with an unexpected PCI related delay.                                                 First author, Dr. Poole, corresponding author, Dr. Hua and colleagues from Shanghai Jiao Tong University in China randomized a total of 344 patients from seven centers to a pharmacoinvasive arm or a primary PCI arm. They found that pharmacoinvasive strategy was non-inferior to primary PCI for the primary endpoint of complete epicardial and myocardial reperfusion after PCI defined as TIMI flow grade 3, TIMI myocardial profusion grade 3, and ST-segment resolution of more than 70%.                                                 There was no significant differences in the frequency of the individual components of the combined endpoint. Infarct size and left ventricular ejection fraction were similar in both groups and there was no significant differences in 30-day rates of total death, re-infarction, heart failure, major bleeding events, or intracranial hemorrhage. However, minor bleeding was observed more often in the pharmacoinvasive group.                                                 Thus the authors concluded that a pharmacoinvasive approach with reduced dose alteplase seems to offer effective and safe reperfusion in low-risk patients with STEMI with an unexpected PCI related delay. Further large, randomized control trials powered for clinical endpoints are needed.                                                 Well, that wraps it up for your summaries. Now for our feature discussion.                                                 The measurement of natriuretic peptides BNP, NT-proNP have certainly become the cornerstone of heart failure management. We measure these levels by guidelines in patients who are presenting with symptoms and suspected heart failure, in patients who are hospitalized. We measure them for prognostication purposes at discharge. However, what we don't really know is how the preceding changes in natriuretic peptides may precede heart failure hospitalization in patients who are at high risk of developing heart failure.                                                 For example, patients with a recent coronary event or type-2 diabetes. And this is the very subject of our feature paper today, and I am so pleased to have the corresponding author of today's paper which is really a research letter. Dr. Brian Claggett from Brigham and Women's Hospital as well as Dr. Biykem Bozkurt who's our senior editor from Baylor College of Medicine.                                                 Welcome both, and maybe I could start, Biykem could you let us know, what are the unanswered questions in heart failure relating to natriuretic peptides and how do you see this paper falling in, clinically? Dr. Biykem Bozkurt:        Carolyn, this is a wonderful I think prelude to perhaps preventing heart failure events. And as you are aware, we in the recent year changed our guidelines at the ACC, AHA, and the HFSA incorporating screening high risk patients for development of incident heart failure. And the study that resulted in this consideration was a STOP-HF trial which was utilizing natriuretic peptides in high risk patients to determine whether their closer follow up in a multidisciplinary fashion would result in earlier detection and prevention of heart failure, and which it did.                                                 And this study I think is straddling the concept of high risk or stage A or B patients because they are individuals who have had heart attacks, coronary events, and they have type-2 diabetes so they are definitely high risk. And doing natriuretic peptides as an outpatient, whether that would predict the heart failure hospitalizations.                                                 And in essence I think it's a good concept. Perhaps the challenging concepts are how often should we screen our patients, and what will be the threshold of the rise that would potentially make us act in either earlier diagnostic strategies, or management strategies. I think those are the two unanswered questions that remains.                                                 How are we gonna screen our patients? Our high risk patients to determine when they are developing heart failure before they become symptomatic? So, what threshold are we going to use? Dr. Carolyn Lam:               That is a perfect set up. I just wanted to add as well in addition to STOP-HF there was the PONTIAC study in diabetics which is very relevant to today's paper that also sort of used NT-proBNP to risk stratify patients for prevention of heart failure. But neither of these studies talked about the temporal changes in natriuretic peptides. And I think a lot of the reason for that is, is that the methods, I mean the statistical methods to do that sort of thing are mind-blowing.                                                 And so Brian, could you now please share with us what you did, the methodology and basically what you found before we discuss the two questions that Biykem brought up? Dr. Brian Claggett:           What was really interesting is the method that we came up with to look at these questions. It's something that we like to believe will be generalizable and can be used in other scenarios and for other biomarkers. But the idea that we have is that we are always used to thinking about the design of a clinical trial as being very regimented. So, you see a patient once at baseline, and then maybe six months later, and then maybe six months after that, and so on. And so it's hard to know what's going on, on a day to day or week to week basis.                                                 But if you think backwards, and you think backwards from the time of any sort of event, because those events whether they're hospitalizations or MIs or death, they happen not on that same schedule. And so odds are at the end of a trial, you had a patient who came to a scheduled visit and then had an event the next day. And you probably had a patient who came in for a visit two days before an event, and another patient who came in a week before an event. So if you start thinking on that time scale, you can piece together all these different time frames when you do have data collected and try to reconstruct something that looks like an actual continuous natural history of what that biomarker would have looked like over say a two year period, if it had been measured continuously. Dr. Carolyn Lam:               So, tell us what you found. First of all, let's just make sure that everyone knows you were looking at the ELIXA cohort, right? Dr. Brian Claggett:           Yes, the data that we had available for this analysis comes from the ELIXA trials, it was 6,068 patients all with type-2 diabetes and a recent ACS event. Recent meaning within the last 180 days. And they were randomized placebo versus a diabetes drug, lixisenatide. And they were followed up for cardiac outcomes.                                                 Beyond that, the natriuretic peptides were measure systematically at baseline, month 6, month 18, and month 24 in all patients who were participating in the trial. So this was the richest collection of a large number of patients being measured multiple times, systematically and not in just a sub-sample of the population. So, we felt like this was a great opportunity to learn something about what happens. What can you learn when you measure these natriuretic peptides over and over again.                                                 And even more interesting than that, the fact that this wasn't a heart failure trial meant that some of the patients already had heart failure at baseline. Other patients didn't have heart failure, but as the trial went on, they developed or were hospitalized for heart failure for the first time. And so we were able to also look at differences between patients experiencing their first heart failure, versus those with more long standing disease. Dr. Carolyn Lam:               And that was very, very unique methodology that you spoke about. And I fully agree that it's going to be used more. I am staring at your beautiful figure one right now. That really, really says it all. Could you walk us through the results? Dr. Brian Claggett:           Sure, I think our key finding is that, I guess no matter when you measure patients. Patients with a higher level of NT-proBNP, or a higher level of BNP at any given time are going to be at higher risk of developing heart failure in the future.                                                 But as we start looking at this as a temporal process, what we see is that there seem to be a noticeable acceleration in these increases, specifically in the last six months before development of heart failure. Or, before a hospitalization for heart failure. And that increase in the final six months seems to occur both in patients who had no prior history of heart failure and also in patients with a history of heart failure. So that six month window I think is something that we learned that we didn't necessarily know before. Dr. Carolyn Lam:               But, going back to Biykem's questions, do you think we have answers to how often we need to survey natriuretic peptides in these high risk patients and what threshold we need to act on? Dr. Brian Claggett:           I think both are very important. I think maybe the timing and the thresholds are somewhat separate questions. I think we're better able to answer the timing question. At the very least we can say that if dramatic changes are happening over a six month window that measuring patients only once every six months probably isn't enough. Whether that means it needs to be every three months, or two months, or one month, or something more than that, I think it's hard to know exactly what the right answer is. But I think we are confident in saying that things happen relatively quickly and we need to be measuring these things more frequently.                                                 As far as the question of thresholds, I think that's maybe even a more difficult question. Or even the idea of a threshold means that we think that there's some magic number and I am not sure that we know for sure what's more important, the absolute number or is it the ... if someone starts relatively low and that relatively low number doubles over the course of six months. That might still be prognostically just as important as someone who's been consistently edging just below or just about that threshold level.                                                 I'm not sure that we're confident enough to say that the changes, the speed of the changes, or the relative changes, or some absolute threshold is the most important thing to be paying attention to. But, I think where these two are related is the more ... that we can start to collect this data more frequently and be able to analyze it. I think that gives us a lot better chance of being able to successfully answer that question about thresholds. Dr. Carolyn Lam:               Indeed. Stuff for future work, huh? Biykem, what do you think? Dr. Biykem Bozkurt:        I wanted to point out two things from Brian's study which was quite interesting. One is the trajectory of the rise, or the delta changes in the natriuretic peptides was quite different in the patients with no history of heart failure compared to those with a history of heart failure. The trajectory, or the linear rise, or the delta changes were more prominent in the individuals with no history of heart failure. Probably intuitively expected so because their baseline levels are not as high as the individuals with history of heart failure.                                                 So, it almost gives the impression that maybe in low low risk, the screening or the frequency may need to be lower, and if low, then probably the likelihood of the rise may be less. But those individuals who, as you said, are edging upward, then maybe the frequency may need to be higher and there may be perhaps a linear rise or a more prominent rise about six months before the incident event.                                                 So, it's an interesting concept just to look at people's trajectories. But, as you said, probably individualization and monitoring or targeting may need to be individualized according to personal risk and other features. And one then wonders futuristically if this would be a concept that would be point of care testing maybe done by the patients similar to glucose monitoring. And in the event that we were to be able to carry the platform to self-test. Dr. Brian Claggett:           You're talking to a statistician, so I am always going to be in favor of collecting more data all the time. So I agree with that. Dr. Carolyn Lam:               Wow, what an insightful discussion. Thank you both for joining us on this podcast today.                                                 Ladies and gentlemen out there, you heard it right here in Circulation on the Run. Tune in again next week.

A discussion with Lou Ezrick, PT and patient who received Bone Marrow Aspirate for his knee pain.  Lou describes his pain, treatment, and response to stem cell derived from bone marrow aspirate. Lou is currently 80% better and is very active.  He is currently working full time managing his physical therapy practice, Evolve Physical Therapy in Brooklyn. Pain physicians interested in learning more about stem cells should contact Dr. Rosenblum via email DRosenblum@QBazaar.com   Patients interested in Stem Cell Therapy are encouraged to schedule an evaluation with David Rosenblum, MD at  Brooklyn Office 6010 Bay Parkway. 6th floor (718) 436 7246 Great Neck Office  (516) 436 7246 DRosenblum@aabpcorp.com   DISCLAIMER: Doctor Rosenblum IS HERE SOLELY TO EDUCATE, AND YOU ARE SOLELY RESPONSIBLE FOR ALL YOUR DECISIONS AND ACTIONS IN RESPONSE TO ANY INFORMATION CONTAINED HEREIN. This video is not intended as a substitute for the medical advice of physician to a particular patient or specific ailment.  You should regularly consult a physician in matters relating to yours or another's health.  You understand that this podcast is not intended as a substitute for consultation with a licensed medical professional.  Copyright © 2017 David Rosenblum All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, recording or otherwise, without the prior written permission of the author.