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In this Bucket List Bit, Greg Shindler cuts through the noise around longevity and wellness trends, sharing what actually works - from high-end treatments to simple daily habits anyone can start tomorrow. He talks candidly about his own morning routine and reveals a fascinating productivity technique that once earned a consultant half a million dollars for just three months of work. If you've ever wondered what health practices are worth your time and money, or you're looking for practical ways to stay sharp and independent as you age, Greg offers refreshingly honest insights that go beyond the usual wellness hype.Listen to the full episode here:Listen on Apple PodcastsListen on SpotifyWatch the Episode On YouTubeLearn more about Greg Shindler
February is American Heart Month, and in light of that, we're bringing back an episode about a group here at Stanford Engineering that's developing 3D printing methods for human tissues and organs, a process known as bioprinting. Motivated in part by the critical need for heart transplants, Mark Skylar-Scott and his team are specifically working to bioprint tissues of the human heart. It may sound like science fiction, but it's actually just another example of the groundbreaking research we do here. We hope you'll take another listen and be inspired by the possibilities.Have a question for Russ? Send it our way in writing or via voice memo, and it might be featured on an upcoming episode. Please introduce yourself, let us know where you're listening from, and share your quest. You can send questions to thefutureofeverything@stanford.edu.Episode Reference Links:Stanford Profile: Mark A. Skylar-ScottMark's Lab: The Skylar-Scott Lab | Stanford MedicineConnect With Us:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads / Bluesky / MastodonConnect with School of Engineering >>> Twitter/X / Instagram / LinkedIn / FacebookChapters:(00:00:00) IntroductionRuss Altman introduces guest, Mark Skylar-Scott, a professor of bioengineering at Stanford University.(00:02:06) What is Bioprinting?The role of cells and biopolymers in printing functional biological structures.(00:03:31) Bioprinting a HeartThe potential of printing organs on demand, especially heart tissue.(00:04:38) Obtaining Cells for BioprintingUsing stem cells derived from the patient's own cells to create heart tissue.(00:06:29) Creating Multiple Cell Types for the HeartThe challenge of printing eleven different heart cell types with precision.(00:08:50) The Scaffold for 3D PrintingThe support material used in 3D printing and how it's later removed.(00:10:10) Cell Migration and Organ FormationHow cells organize themselves to form functional heart tissue.(00:12:08) Growing a Full-Sized HeartWhether they're printing full-sized hearts or starting with smaller organs.(00:13:34) Avoiding Overgrowth RisksThe role of bioreactors in shaping the early stages of the organ.(00:14:57) Scaling Up Cell ProductionThe need to generate massive numbers of cells for experimentation.(00:18:32) The Challenge of VascularizationCreating a blood vessel network to supply oxygen and nutrients.(00:22:35) Ethical Considerations in BioprintingConsent, stem cell sourcing, and the broader ethical landscape.(00:26:04) The Timeline for Bioprinted OrgansThe long timeline for bioprinted organs to reach clinical use.(00:27:24) The State of the Field & CollaborationThe collaborative, competitive biofabrication field and its rapid progress.(00:28:20) Conclusion Connect With Us:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads / Bluesky / MastodonConnect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook
Electro-Agriculture “Scientists Grow Crops in Near-Total Darkness Thanks to New ‘Electro-Agriculture' Technique.” by Adam Kovac. 2024 “Electro-agriculture: Revolutionizing farming for a sustainable future.” by Bradie S. Crandall, Marcus Harland-Dunaway, Robert E. Jinkerson, et al. 2024 Space Exploration with Dr. Robert Lillis“An ESCAPADE to Mars, on the cheap.” The Planetary Society. 2021.“ESCAPADE: Mission to Mars.” Rocketlab. “Mission to Mars - ESCAPADE.” Rocketlab.“Dr. Rob Lillis.” Harvath Law Group. “MAVEN Maps Electric Currents around Mars that are Fundamental to Atmospheric Loss.” by William Steigerwald. 2020. Stem Cell Vision Repair “Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan.” by Takeshi Soma, Yoshinori Oie, Hiroshi Takayanagi, Shoko Matsubara, et al. 2024 “World First: Stem Cell Transplant Restores Vision in Multiple People.” by Carly Cassella. 2024. “Stem cell transplant shows promise for vision loss.” by Rebecca Turner. 2024.“Limbal Stem Cell Deficiency.” ColumbiaDoctors. “Induced Pluripotent Stem Cells.” UCLA Broad Stem Cell Research Center. Newscast Soundbites Mars ExplorationFollow Curiosity Weekly on your favorite podcast app to get smarter with Dr. Samantha Yammine — for free! Still curious? Get science shows, nature documentaries, and more real-life entertainment on discovery+! Go to https://discoveryplus.com/curiosity to start your 7-day free trial. discovery+ is currently only available for US subscribers. Hosted on Acast. See acast.com/privacy for more information.
In this podcast, we spoke with Dr. Jorge Escobar Ivirico, Product Manager, Bioprocess Solutions at Eppendorf, about the fascinating world of induced pluripotent stem cells (iPSCs), exploring their groundbreaking potential in regenerative medicine, personalized therapies, and drug development. Our guest explained how iPSCs, created by reprogramming adult somatic cells, can differentiate into virtually any cell type, making them invaluable for research and therapeutic applications. We delved into the importance of consistency, quality control, and reproducibility in iPSC production, alongside the challenges of culturing these cells, such as maintaining pluripotency and scaling production for clinical use. The discussion highlighted exciting advancements, including the development of organoids and universal T cells, as well as the ethical considerations distinguishing iPSCs from embryonic stem cells. Looking to the future, Jorge envisioned iPSCs becoming a cornerstone of standard medical practice, while acknowledging the need to address safety, scalability, and regulatory hurdles to fully realize their potential. What are Induced Pluripotent Stem Cells (iPSCs)? "Induced pluripotent stem cells are a type of stem cell created by reprogramming adult somatic cells, like skin or blood cells, back into an embryonic-like state," explains Jorge. This process involves introducing specific transcription factors, often called Yamanaka factors, to transform these cells into a versatile state. Once reprogrammed, iPSCs can differentiate into almost any cell type, making them invaluable tools for research, drug development, and potentially life-changing therapies. The Growing Importance of iPSCs iPSCs offer a range of advantages, particularly their ability to sidestep ethical concerns tied to embryonic stem cell use. “What makes iPSCs so important today,” Jorge notes, “is their versatility and potential applications. Researchers can create patient-specific cell lines, which are essential for drug screening, disease modeling, and personalized medicine.” This technology is pivotal for regenerative medicine, offering hope for repairing damaged tissues and organs. “From neurodegenerative diseases to heart damage, iPSCs open the door to innovative treatment possibilities,” he adds. Mastering the Production Process Producing iPSCs is a meticulous endeavor. "Consistency is key," emphasizes Jorge. Researchers must ensure that each batch of cells meets strict criteria to avoid unpredictable outcomes, especially when precision is vital in both research and therapeutic applications. Standardized protocols and quality control measures are essential to achieve consistency. These involve monitoring for contamination and verifying the cells' ability to differentiate into various cell types. “Imagine developing a therapy based on a specific batch of cells, only to find that subsequent batches behave differently,” he warns. “Such inconsistencies can jeopardize patient outcomes.” Tackling Challenges in Culturing iPSCs Culturing iPSCs presents its own set of challenges. High cell numbers are often needed for large-scale research or therapeutic applications, but scaling up production without compromising quality is no small feat. Maintaining the cells' pluripotent state is another hurdle, as they can easily differentiate prematurely under certain culture conditions. "Environmental parameters like temperature, pH, oxygen levels, and nutrient availability must be rigorously controlled," Jorge explains. “Even minor fluctuations can negatively impact cell health and their ability to remain pluripotent.” Innovations Addressing Culturing Hurdles To overcome these challenges, researchers are turning to advanced techniques like 3D culture systems and bioreactors. These provide a more natural growth environment for the cells, enhancing their viability and functionality. “By transitioning from traditional 2D cultures to 3D systems,
Join Fazale “Fuz” Rana and Hugh Ross as they discuss new discoveries taking place at the frontiers of science that have theological and philosophical implications, including the reality of God's existence. Growing Human Organs in Pigs In the fall of 2023, a team of researchers from China published the results of a proof-of-principle study that demonstrated for the first time that it's possible to grow humanized kidneys in a fetal pig. This work provides the means to study the process of organogenesis that may also alleviate the shortage of organs available for human transplant procedures. However, this research raises all sorts of questions that could be summarized with a single question: “Should we play God?” In this episode, biochemist Fuz Rana describes the work of the Chinese researchers and offers a Christian perspective on the creation of human-animal chimeras. Mitigating Air Pollution Air pollution level in India's capital territory of Delhi is more than 25 times greater than the maximum human tolerable level set by the World Health Organization (WHO). This pollution is called PM2.5 (inhalable particles with diameters of 2.5 micrometers or less) and is almost entirely composed of black carbon soot, mineral dust, sulfates, nitrates, ammonia, and sodium chloride. Scientists at WHO have determined that the average Indian living in Delhi would live 11.9 years longer if the PM2.5 level there were reduced to WHO's maximum limit. Nearly all of India's PM2.5 air pollution comes from the burning of coal, wood, biomass, diesel, gasoline, and oil, in that order. Replacing these fuel sources with natural gas would eliminate all of India's PM2.5 except for the small contribution from road and construction dust. This replacement would also immediately reduce carbon greenhouse gas emissions by nearly half. PODCAST LINKS: Generation of a Humanized Mesonephros in Pigs from Induced Pluripotent Stem Cells via Embryo Complementation Additional Resources: A Theology for Synthetic Biology, Part 1 A Theology for Synthetic Biology, Part 2 YOUTUBE LINKS: Jiaowei Wang et al., “Generation of a Humanized Mesonephros in Pigs from Induced Pluripotent Stem Cells via Embryo Complementation,” https://pubmed.ncbi.nlm.nih.gov/37683604/ Additional Resources: Fazale Rana, “A Theology for Synthetic Biology, Part 1,” https://reasons.org/explore/publications/articles/a-theology-for-synthetic-biology-part-1-of-2 Fazale Rana, “A Theology for Synthetic Biology, Part 2,” https://reasons.org/explore/publications/articles/a-theology-for-synthetic-biology-part-2-of-2 PODCAST LINKS: Air Quality Life Index 2023: Annual Update (August 2023) Air Quality Life Index, India Fact Sheet (2023) The Relationship between Fine Particle Matter (PM2.5) Exposure and Upper Respiratory Tract Diseases YOUTUBE LINKS: Michael Greenstone and Christa Hasenkopf, Air Quality Life Index 2023: Annual Update (August 2023),https://aqli.epic.uchicago.edu/wp-content/uploads/2023/08/AQLI_2023_Report-Global.pdf Air Quality Life Index, India Fact Sheet (2023), https://aqli.epic.uchicago.edu/wp-content/uploads/2023/08/India-FactSheet-2023_Final.pdf Łukasz Zaręba et al., “The Relationship between Fine Particle Matter (PM2.5) Exposure and Upper Respiratory Tract Diseases,” https://www.mdpi.com/2075-4426/14/1/98
Joseph Wu, MD, PhD discusses how stem cells are being employed to better understand mechanisms of cancer therapy-related cardiotoxicity. Moderated by Nicholas Wilcox, MD, MHS.
Is ageing a conquerable disease?Join host Trav Bell and Longevity CEO & Cellular Medicine Entrepreneur Greg Shindler as they dive into the world of healthcare, stem cell treatments, and the pursuit of healthier ageing. In this engaging conversation, discover the fascinating science of stem cells, the role of lifestyle factors in promoting longevity, and the necessary mindset shift to approach ageing as a disease. But it's not all science and research – Greg shares his personal journey of resilience, survival, and the pursuit of a meaningful life. Get ready for an inspiring discussion on the keys to living longer, healthier, and purposefully. Tune in to the podcast now!Episode Highlights:"What happens to you in life is not near as important as what you do about it.” — Greg Shindler"Data shows that people who did live longer typically were more intimate later in life than those who weren't.” — Greg Shindler“There's no silver bullet for living healthier longer, period. You gotta put in the work.” — Greg Shindler“The primary goal is really about that functional decline, trying to keep that as intact as possible for as long as possible. And I think that's the right goal, quite frankly.” — Greg Shindler“Just be curious. When we're curious, it opens more doors.” — Greg Shindler“With any goal that you've got in life, you can easily get overwhelmed. I've always said to people to pick a handful, I reckon 3, 4 max thought leaders in the space and just say no to everyone else and let and just go deep on their stuff.” — Trav BellConnect with Greg Shindler:Website - https://gregshindler.com/Facebook - https://www.facebook.com/gslongevitywarriorLinkedIn - https://www.linkedin.com/in/gregory-shindler-aa62b84b/Instagram - https://www.instagram.com/gregshindler/Regenerative Medicine Institute - https://www.rmi-international.com/Connect with Trav Bell:Website - https://www.thebucketlistguy.com/LinkedIn - https://www.linkedin.com/in/travbell/Facebook - https://www.facebook.com/thebucketlistguyTwitter - https://twitter.com/TravBellInstagram - https://www.instagram.com/bucketlistguy.travbell/YouTube - https://www.youtube.com/user/TheBucketListGuy2011Podcast - https://podcasts.apple.com/us/podcast/the-bucket-list-life-helping-you-build-a-life-by-design/id1712886116Book - www.thebucketlistguy.com/book
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.18.549581v1?rss=1 Authors: Nguyen, V., Kravitz, J., Gao, C., Hochman, M. L., Meng, D., Chen, D., Wang, Y., Jegga, A. G., Nelson, S., Tan, W. Abstract: Port Wine Birthmark (PWB) is a congenital vascular malformation in the skin, occurring in 1-3 per 1,000 live births. We recently generated PWB-derived induced pluripotent stem cells (iPSCs) as clinically relevant disease models. The metabolites associated with the pathological phenotypes of PWB-derived iPSCs are unknown, which we aimed to explore in this study. Metabolites were separated by ultra-performance liquid chromatography and were screened with electrospray ionization mass spectrometry. Orthogonal partial least-squares discriminant analysis, multivariate and univariate analysis were used to identify differential metabolites (DMs). KEGG analysis was used for the enrichment of metabolic pathways. A total of 339 metabolites were identified. There were 22 DMs confirmed with 9 downregulated DMs including sphingosine and 13 upregulated DMs including glutathione in PWB iPSCs as compared to controls. Pathway enrichment analysis confirmed the upregulation of glutathione and downregulation of sphingolipid metabolism in PWB-derived iPSCs as compared to normal ones. We next examined the expression patterns of the key factors associated with glutathione metabolism in PWB lesions. We found that hypoxia-inducible factor 1 (HIF1), glutathione S-transferase Pi 1 (GSTP1), {gamma}-glutamyl transferase 7 (GGT7), and glutamate cysteine ligase modulatory subunit (GCLM) were upregulated in PWB vasculatures as compared to blood vessels in normal skins. Our data demonstrate that there are perturbations in sphingolipid and cellular redox homeostasis in the PWB vasculature, which may facilitate cell survival and pathological progression. Our data imply that upregulation of glutathione may contribute to laser-resistant phenotypes in the PWB vasculature. 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/2023.07.02.547408v1?rss=1 Authors: Nguyen, V., Gao, C., Hochman, M., Kravitz, J., Chen, E., Friedman, H., Wenceslau, C., Chen, D., Wang, Y., Nelson, J. S., Jegga, A. G., Tan, W. Abstract: Background: Port Wine Birthmark (PWB) is a congenital vascular malformation resulting from developmentally defective endothelial cells (ECs). Developing clinically relevant disease models is an unmet need for PWB studies. Objective: This study aims to generate PWB-derived induced pluripotent stem cells (iPSCs) and those-iPSC-derived ECs that preserve disease-related phenotypes. Method: PWB iPSCs were generated by reprogramming lesional dermal fibroblasts and were differentiated into ECs. Bulk RNA-seq and ATAC-seq were performed to identify enriched pathways. The functional phenotypes of iPSC-derived ECs were characterized using capillary-like structure (CLS) formation in vitro and Geltrex plug-in assay in vivo. Result: Human PWB and normal iPSC lines were generated through reprogramming of dermal fibroblasts by introducing the Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) into them; The iPSCs were differentiated into ECs. These iPSCs and their-derived ECs were validated by expression of series of stem cell and EC biomarkers, respectively. PWB EC showed impaired CLS in vitro with larger perimeters and thicker branches comparing with control iPSC-derived ECs. In plug-in assay, perfused human vasculature formed by PWB iPSC-derived ECs showed bigger perimeters and greater densities than those formed by control iPSC-derived ECs in SCID mice. The transcriptome analysis showed that the impaired pathways of stem cell differentiation, Hippo, Wnt, and focal adhersion persisted through PWB iPSCs to ECs during differentiation. Interactive networks showed that the Hippo and Wnt pathway-related differentially expressed genes (DEGs) significantly function in vasculature development, tube morphology, endothelium development, and EC differentiation. Members of zinc-finger (ZNF) gene family were among the top changed DEGs in both PWB iPSCs and ECs. The ZNF DEGs confer significant functions in transcriptional regulation, chromatin remodeling, protein ubiquitination, and retinol acid pathway. In addition, NF-kappa B, TNF, MAPK, and cholesterol metabolism pathways were upregulated in PWB ECs as readouts of impaired differentiation. Conclusion: PWB iPSC-derived ECs can be served as novel and clinically relevant disease models by retaining pathological phenotypes. Our data suggests the impaired Hippo and Wnt pathways underlie the development of differentiation-defective ECs in PWB lesions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Thank you Joshua Hansen, OMS III, Quin Gray, OMS III and Doug Wirthlin, OMS III for joining me in a conversation regarding the exciting future of psychiatry. This podcast describes how induced Pluripotent Stem Cells may affect psychiatry in the future. This does not have any shelf-prep, but we found the topic interesting enough to plan for additional episodes. We enjoyed our discussion and hope you do too! Thank you to the immortal Jordan Turner for creating the perfect bumper music!
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.06.535946v1?rss=1 Authors: Bhowmik, A. T., Zhao, S. R., Wu, J. C. Abstract: Electronic cigarettes (e-cigarettes) have become increasingly popular with adolescents in recent years as a result of aggressive marketing schemes, false safety claims, and appealing flavors targeted towards teens from e-cigarette companies. In the past 8 years alone, e-cigarette use amongst youth has increased by 18 times. Although many dangerous effects of smoking e-cigarettes on lungs have come to light, limited and qualitative effort has been made to analyze the impact of smoking e-cigarettes on the human heart directly. In this study, we determined e-liquid cardiotoxicity in both healthy cells and cells with long QT syndrome by treating healthy and diseased human cardiomyocytes with e-liquids with varying nicotine concentrations. These cardiomyocytes were generated from human induced pluripotent stem cells. The cardiomyocytes were divided into 5 groups, a control group and 4 test groups, each treated with e-liquid containing varying amounts of nicotine between 0% and 70%. The cells' biological indicators such as heart rate, pulse pressure, essential protein concentration, and metabolic activity, were measured, characterized using three different functional assays: contractility, Western blot, and viability, and tracked closely over 2 weeks. The results demonstrated that acute exposure to e-liquid led to tachycardia, hypertension, decreased protein levels, and cell death. The rate of cardiotoxicity increases with higher nicotine concentrations. The basal fluid also showed non-negligible toxicity. Under identical conditions, the functionality of the diseased heart cells declined at a faster rate compared to healthy cells. Overall, this work systematically establishes the harmful physiological effects of e-cigarettes on the human heart quantitatively. 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/2023.02.22.529606v1?rss=1 Authors: Lam, Y. Y., Chan, C. H., Geng, L., Wong, N., Keung, W., Cheung, Y. F. Abstract: Cardiomyocytes can be readily derived from human induced pluripotent stem cell (hiPSC) lines, yet its efficacy varies across different batches of the same and different hiPSC lines. To unravel the inconsistencies of in vitro cardiac differentiation, we utilized single cell transcriptomics on hiPSCs undergoing cardiac differentiation and identified cardiac and extra-cardiac lineages throughout differentiation. We further identified APLNR as a surface marker for in vitro cardiac progenitors and immunomagnetically isolated them. Differentiation of isolated in vitro APLNR+ cardiac progenitors derived from multiple hiPSC lines resulted in predominantly cardiomyocytes accompanied with cardiac mesenchyme. Transcriptomic analysis of differentiating in vitro APLNR+ cardiac progenitors revealed transient expression of cardiac progenitor markers before further commitment into cardiomyocyte and cardiac mesenchyme. Analysis of in vivo human and mouse embryo single cell transcriptomic datasets have identified APLNR expression in early cardiac progenitors of multiple lineages. This platform enables generation of in vitro cardiac progenitors from multiple hiPSC lines without genetic manipulation, which has potential applications in studying cardiac development, disease modelling and cardiac regeneration. 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/2023.02.02.526657v1?rss=1 Authors: May, A., Ventura, T., Fidanza, A., Volmer, H., Taylor, H. A., Romano, N., D'Souza, S. L., Bieker, J. J., Forrester, L. M. Abstract: Congenital dyserythropoietic anaemia (CDA) type IV has been associated with an amino acid substitution, Glu325Lys (E325K), in the transcription factor KLF1. These patients present with a range of symptoms, including the persistence of nucleated red blood cells (RBCs) in the peripheral blood which reflects the known role for KLF1 within the erythroid cell lineage. The final stages of RBCs maturation and enucleation take place within the erythroblastic island (EBI) niche in close association with EBI macrophages. It is not known whether the detrimental effects of the E325K mutation in KLF1 are restricted to the erythroid lineage or whether deficiencies in macrophages associated with their niche also contribute to the disease pathology. To address this question, we generated an in vitro model of the human EBI niche using induced pluripotent stem cells (iPSCs) derived from a CDA type IV patient as well as iPSCs genetically modified to express an KLF1-E325K-ERT2 protein that could be activated with 4OH-tamoxifen. CDA patient-derived iPSCs and iPSCs expressing the activated KLF1-E325K-ERT2 protein showed significant deficiencies in the production of erythroid cells with associated disruption of some known KLF1 target genes. Macrophages could be generated from all iPSC lines but when the E325K-ERT2 fusion protein was activated, we noted the generation of a slightly less mature macrophage population marked by CD93. A subtle reduction in their ability to support RBC maturation was also associated with macrophages carrying the E325K-ERT2 transgene. Taken together these data support the notion that the clinically significant effects of the KLF1-E325K mutation are primarily associated with deficiencies in the erythroid lineage but that deficiencies in the niche might have the potential to exacerbate the condition. The strategy we describe provides a powerful approach to assess the effects of other mutations in KLF1 as well as other factors associated with the EBI niche. 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/2023.01.19.524780v1?rss=1 Authors: Estep, K. N., Tobias, J. W., Fernandez, R. J., Beveridge, B. M., Johnson, F. B. Abstract: Although mechanisms of telomere protection are well-defined in differentiated cells, it is poorly understood how stem cells sense and respond to telomere dysfunction. Recent efforts have characterized the DNA damage response (DDR) following progressive telomere erosion in human pluripotent cells, yet the broader impact of telomeric double-strand breaks (DSBs) in these cells is poorly characterized. Here, we report on DNA damage signaling, cell cycle, and transcriptome-level changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineered a novel human iPSC line with a targeted doxycycline-inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DDR in iPSCs, in contrast to an established ATM-dependent response to telomeric FokI breaks in differentiated cells. ATR activation leads to a potent cell cycle arrest in G2, which we show is p53-independent and can be rescued by treatment with an ATR inhibitor. Telomere lengths are remarkably well-maintained in the face of persistent TRF1-FokI induction. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase, we show that telomerase is largely dispensable for survival and telomere length maintenance following telomeric breaks, which instead appear to be repaired by a mechanism bearing hallmarks of lengthening mediated by homologous recombination, so-called alternative lengthening of telomeres (ALT). Our findings suggest a previously unappreciated role for ALT in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric damage. 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/2023.01.03.522057v1?rss=1 Authors: Nakajima, I., Tsukimura, T., Ono, T., Shiga, T., Shitara, H., Togawa, T., Sakuraba, H., Miyaoka, Y. Abstract: Human induced pluripotent stem cells (iPSCs) have already been used in transplantation therapies. Currently, cells from healthy people are transplanted into patients with diseases. With the rapid evolution of genome editing technology, genetic modification could be applied to enhance the therapeutic effects of iPSCs, such as the introduction of secreted molecules to make the cells a drug delivery system. Here, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the lack of -Galactosidase A (GLA). We previously developed an immunotolerant therapeutic molecule, modified -N-acetylgalactosaminidase (mNAGA). We confirmed that secreted mNAGA from genome-edited iPSCs compensated for the GLA activity in GLA-deficient cells using an in vitro co-culture system. Moreover, iPSCs transplanted into Fabry model mice secreted mNAGA and supplied GLA activity to the liver. This study demonstrates the great potential of genome-edited iPSCs secreting therapeutic molecules. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Daniel Teper is the CEO and Founder of Cytovia Therapeutics and talks about using natural killer, NK, cells as an alternative to T-cells in immuno-oncology. He shares insights about the development of induced pluripotent stem cells, IPSC-derived NK cells, iNK cells, used by themselves or using their Flex-NK cell Engagers or in combination to address the challenges cancer patients face. Daniel elaborates, "That's also where the NK cells may have advantages over T-cells, in that it hasn't been reported that they cause CRS, GBHD, or other side effects that would require the patients to be kept in the hospital. Now, if we say the first iteration was derived from the patient's own blood, the second iteration is donor, the third generation, which we are one of a handful of companies to pursue and master, is the production of immune cells, including NK cells, from induced pluripotent stem cells." "We see also that you can direct the cells in two ways. You can direct the cells by inserting what's called a CAR, or chimeric antigen receptor, that's like a GPS on the cell. But alternatively, we can redirect the NK cells to kill the tumor cells by combining them with antibodies, and particularly with what we call NK engager antibodies. So our brand of NK engager antibodies is called Flex-NK cell engager antibodies. And what they do is that they have one arm that binds and activates the NK cell, and another arm that binds into the tumor cell, and the NK cells are redirected to kill the tumor cells." @Cytovia #CytoviaTX #Oncology #ImmunoOncology #Cancer #CancerTherapeutics #CellTherapeutics #NKCells #iNKCells #NaturalKillerCells CytoviaTX.com Download the transcript here
Daniel Teper is the CEO and Founder of Cytovia Therapeutics and talks about using natural killer, NK, cells as an alternative to T-cells in immuno-oncology. He shares insights about the development of induced pluripotent stem cells, IPSC-derived NK cells, iNK cells, used by themselves or using their Flex-NK cell Engagers or in combination to address the challenges cancer patients face. Daniel elaborates, "That's also where the NK cells may have advantages over T-cells, in that it hasn't been reported that they cause CRS, GBHD, or other side effects that would require the patients to be kept in the hospital. Now, if we say the first iteration was derived from the patient's own blood, the second iteration is donor, the third generation, which we are one of a handful of companies to pursue and master, is the production of immune cells, including NK cells, from induced pluripotent stem cells." "We see also that you can direct the cells in two ways. You can direct the cells by inserting what's called a CAR, or chimeric antigen receptor, that's like a GPS on the cell. But alternatively, we can redirect the NK cells to kill the tumor cells by combining them with antibodies, and particularly with what we call NK engager antibodies. So our brand of NK engager antibodies is called Flex-NK cell engager antibodies. And what they do is that they have one arm that binds and activates the NK cell, and another arm that binds into the tumor cell, and the NK cells are redirected to kill the tumor cells." @Cytovia #CytoviaTX #Oncology #ImmunoOncology #Cancer #CancerTherapeutics #CellTherapeutics #NKCells #iNKCells #NaturalKillerCells CytoviaTX.com Listen to the podcast here
One of our most powerful new tools in recent years for in vitro experiments are something called induced pluripotent stem cells, or iPSCs. iPSCs are created with a technique that allows scientists to take living cells, often skin cells, from an adult human and revert them to the state of a stem cell, which can then be grown into any kind other kind of cell in the body – including cells affected by ALS like motor neurons. To further explain what an iPSC is and how we use them in our research to end ALS, we're joined today by Dr. Kyle Denton, ALS TDI's director of Cell biology. Support the show: https://www.als.net/donate/ See omnystudio.com/listener for privacy information.
We’d love to hear from you (feedback@breakingbadscience.com)Look us up on social media Facebook: https://www.facebook.com/groups/385282925919540Instagram: https://www.instagram.com/breakingbadsciencepodcast/Website: http://www.breakingbadscience.com/Patreon: https://www.patreon.com/breakingbadscienceStem cells are a mysterious cellular construct with some pretty unique properties. Properties which have led to intense discussions about life, aging, cancer, the nature of disease itself, and even religion. But what are they? Why was the discovery of these cells so important? Why are they so controversial and how has that controversy affected research in the last few decades? Join hosts Shanti and Danny as we discuss stem cells, the confusion surrounding them, and why the controversy is not only important but necessary in this episode of Breaking Bad Science. ReferencesPlatt, A.; A Brief History of U.S. Stem Cell Policy. Research America. 2020. https://www.researchamerica.org/advocacy-action/issues-researchamerica-advocates/stem-cell-research/brief-history-us-stem-cellHwang, N., et. al.; Controlled Differentiation of Stem Cells. Advanced Drug Delivery Reviews. 11-Oct-2007. 60:2 (199 - 214). Doi: https://doi.org/10.1016/j.addr.2007.08.036Robinton, D., Daley, G.; The Promise of Induced Pluripotent Stem Cells in Research and Therapy. Nature. 18-Jan-2012. 481 (295 - 305). Doi: https://doi.org/10.1038/nature10761Chin, M., et. al.; Induced Pluripotent Stem Cells and Embryonic Stem Cells are Distinguished by Gene Expression Signatures. Cell - Stem Cell. 2-Jul-2009. 5:1 (111 - 123). Doi: https://doi.org/10.1016/j.stem.2009.06.008Biehl, J., Russell, B.; Introduction to Stem Cell Therapy. Journal of Cardiovascular Nursing. Mar/Apr-2009. 24:2 (98 - 105). Doi: https://doi.org/10.1097/JCN.0b013e318197a6a5Ayala, F.; Cloning Humans? Biological, Ethical, and Social Considerations. PNAS. 21-Jul-2015. 112:29 (8879 - 8886). Doi: https://doi.org/10.1073/pnas.1501798112Hernandez, D.; 500 Years Later, da Vinci’s Mechanical Lion is Brought to Life. Popular Mechanic. 19-Sep-2019. https://www.popularmechanics.com/technology/a29020685/leonardo-da-vinci-mechanical-lion-display/Ayob, A., Ramasamy, T.; Cancer Stem Cells as Key Drivers of Tumour Progression. Journal of Biomedical Science. 06-Mar-2018. 25:20. Doi: https://doi.org/10.1186/s12929-018-0426-4Kim, K.S.; Converting Human Skin Cells to Neurons: A New Tool to Study and Treat Brain Disorders? Cell - Stem Cell. 2-Sep-2011. 9:3 (179 - 181). Doi: https://doi.org/10.1016/j.stem.2011.08.004Support the show (https://www.patreon.com/breakingbadscience?fan_landing=true)
Yamanaka Factors for the Cardio-Oncologist Dr RR Baliga's 'Got Knowledge Doc' Podkasts for Physicians Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663-76. doi: 10.1016/j.cell.2006.07.024. Epub 2006 Aug 10. PMID: 16904174. Sharma A. Stem cells to help the heart. Science. 2020 Mar 13;367(6483):1206. doi: 10.1126/science.aba6111. PMID: 32165579. Sayed N, Ameen M, Wu JC. Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell. Cardiovasc Res. 2019 Apr 15;115(5):949-959. doi: 10.1093/cvr/cvz024. PMID: 30768178; PMCID: PMC6933506. Yoshida Y, Yamanaka S. Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications. Circ Res. 2017 Jun 9;120(12):1958-1968. doi: 10.1161/CIRCRESAHA.117.311080. PMID: 28596174. Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020 Dec;588(7836):124-129. doi: 10.1038/s41586-020-2975-4. Epub 2020 Dec 2. PMID: 33268865. Litviňuková M, Talavera-López C, Maatz H, Reichart D, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann ER, Roberts K, Tuck L, Fasouli ES, DeLaughter DM, McDonough B, Wakimoto H, Gorham JM, Samari S, Mahbubani KT, Saeb-Parsy K, Patone G, Boyle JJ, Zhang H, Zhang H, Viveiros A, Oudit GY, Bayraktar OA, Seidman JG, Seidman CE, Noseda M, Hubner N, Teichmann SA. Cells of the adult human heart. Nature. 2020 Sep 24:1–7. doi: 10.1038/s41586-020-2797-4. Epub ahead of print. PMID: 32971526; PMCID: PMC7681775.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.20.162040v1?rss=1 Authors: Chen, H., Thakkar, A., Cross, A., Xu, H., Li, A., Pauli, D., Noggle, S. A., Kruger, L., Denton, T. T., Gibson, G. E. Abstract: The coupling of the endoplasmic reticulum (ER) with mitochondria modulates neuronal calcium signaling. Whether this link changes with neuronal development is unknown. The current study first determined whether ER calcium stores are similar during development of human neurons, and then tested if the ER/mitochondrial coupling varied with development. The release of ER calcium to the cytosol by the IP3 agonist bradykinin was determined in human induced-pluripotent stem cells (iPSC), neural stem cells (NSC) and neurons. The concentration dependence for the release of ER calcium was similar at different stages of development. Metabolism changes dramatically with development. Glycolysis is the main energy source in iPSC and NSC whereas mitochondrial metabolism is more prominent in neurons. To test whether the coupling of mitochondria and ER changed with development, bombesin or bradykinin releasable calcium stores (BRCS) were monitored after inhibiting either of two key mitochondrial enzyme complexes: the alpha-ketoglutarate dehydrogenase complex (KGDHC) or the pyruvate dehydrogenase complex (PDHC). Inhibition of KGDHC did not alter BRCS in either iPSC or NSC. Inhibition of PDHC in neurons diminished BRCS whereas decreased KGDHC activity exaggerated BRCS. The latter finding may help understand the pathology of Alzheimers disease (AD). BRCS is exaggerated in cells from AD patients and KGDHC is reduced in brains of patients with AD. In summary, a prominent ER/mitochondrial link in neurons is associated with selective mitochondrial enzymes. The ER/mitochondrial link changes with human neuronal development and plausibly links ER calcium changes to AD. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.135392v1?rss=1 Authors: Duong, A., Evstratova, A., Sivitilli, A., Hernandez, J. J., Gosio, J., Wahedi, A., Sondheimer, N., Wrana, J. L., Beaulieu, M., Attisano, L., Andreazza, A. Abstract: Mitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples. Copy rights belong to original authors. Visit the link for more info
Topic Discussed : Global Cell Therapy MarketSpeaker: Aarti ChitaleKey Takeaways:This report covers the key trends and opportunities across the global cell therapy market. Some of the key areas being covered under the market include, industry trends, manufacturing automation, combination therapies and other future trends The report also highlights some of the emerging business models benefiting the market as well as the key drivers and restraints affecting the market growthWith the changing market landscape, Big pharma/bio-pharma players, are looking towards the adoption of a collaborative business approach by either entering into co-development/ co-commercialization agreements or acquiring smaller niche players so as to achieve competitive advantage with respect to specific therapy area or technologyAdditionally, in order to cater to the pricing needs of these high value therapies, the companies are adopting a pay for performance model which allows the payer to make a payment basis the therapeutic outcome of the novel therapyKymriah and yescarta are amongst the first such CAR-T cell therapies with this arrangement. Also, there is a large scale adoption of risk sharing, fast to market models, which supports the development of these novel therapiesFor further insights, please join us for future podcasts and become a member of Frost & Sullivan’s Leadership Council by emailing us at: digital@frost.com or click here to Contact Us.Related Keywords: Frost & Sullivan, Regenerative Medicine, Combination Therapies, Cell-Gene therapies, Stem Cell Therapies, Mesenchymal Stem Cells, Adipose Derived Stem Cells, Induced Pluripotent Stem Cells, European Medicines Agency, Food and Drug Administrations, Act for Safety of Regenerative Medicine, Pharmaceutical and Medical Devices Act, CRISPR/Cas9, ACR-T Cell Therapies, Kymriah, Yescarta, Gilead Sciences, Novartis, Mergers and Acquisitions, Genome Editing, Curative Therapies, Nano-medicine, Alternative payment Models, One-time Payment Model, Annuity Payment Model, Value Based Payment Model, Autologous Stem Cells, Allogeneic Stem Cells, Fast to Market Model, Risk Sharing Model, In-House Development, Competitive Playbook, Conditional Approval, Oncology, Neurology, Cardiovascular Diseases, Dermatology, Muscoloskeletal, ImmunologyWebsite: www.frost.com See acast.com/privacy for privacy and opt-out information.
Human stem cells were once viewed primarily as regenerative materials for tissue repair through cell therapies. However, advances in technologies and protocols mean that induced pluripotent stem cells (iPSCs) are now playing an increasingly important role in disease modelling and human cell-based screening assays. This episode explores what this means for drug discovery. The pharmaceutical industry’s current issue with attrition in the R&D pipeline is complex and multifaceted. However, few would disagree that one of the biggest factors contributing to the poor rate of success in drug discovery is the lack of reliable and translationally useful disease models. No matter how carefully studies are designed, animal models and immortalised cell lines cannot reflect the full complexity of human biology and disease mechanisms. While the use of human primary cells or human tissue samples is an attractive alternative for drug screening, these materials can be difficult to obtain, and require additional ethical considerations. Original article by Abby Edwards and Dr Richard Massey, of Biostrata If you'd like to view the original article then follow the link below: https://www.ddw-online.com/screening/p322574-unlocking-the-full-potential-of-induced-pluripotent-stem-cells-for-drug-discovery.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133164/(5)-unlocking-the-full-potential-of-induced-pluripotent-stem-cells.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com
Monica Nizzardo, University of Milan, IRCCS Cà Granda Foundation, Ospedale Maggiore Policlinico, Milan, ITALY speaks on "Induced pluripotent stem cells for ALS: in vitro disease model and source of transplantation". This movie has been recorded by ICGEB Trieste.
Reading by Joseph Wu, MD, and Kitchener Wilson, MD, author of Induced Pluripotent Stem Cells
The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to John B. Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent
On Wednesday 12th September 2012 we hosted a live induced pluripotent stem cell event. The event was broadcast across Europe so scientists could watch it live. The speakers were Monika Madej (University of Cambridge), Leopoldo Laricchia-Robbio (CMRB Barcelona) and Marisa Jaconi (University of Geneva). Please visit www.lifetechnologies.com/LifeiPSC2012
On Wednesday 12th September 2012 we hosted a live induced pluripotent stem cell event. The event was broadcast across Europe so scientists could watch it live. The speakers were Monika Madej (University of Cambridge), Leopoldo Laricchia-Robbio (CMRB Barcelona) and Marisa Jaconi (University of Geneva). Please visit www.lifetechnologies.com/LifeiPSC2012
You might have seen: PhysOrg, "Induced pluripotent stem cells at risk for rejection" May 13, 2011; http://www.physorg.com/news/2011-05-therapies-pluripotent-stem-cells-encounter.html
In this NewsFlash, tailor made proteins that bind to 'flu viruses, the largest gathering of whale sharks in the world, and how induced stem cells may be rejected, even by genetically identical animals. Plus, how a laser technique has shed new light on a common process that leads to cancer.
Enhanced Video PodcastAired date: 7/26/2010 3:00:00 PM Eastern Time
Enhanced Audio PodcastAired date: 7/26/2010 3:00:00 PM Eastern Time
Scientific American Editor in Chief Mariette DiChristina talks with podcast host Steve Mirsky about the contents of the May issue, including articles on induced pluripotent stem cells, high-speed and maglev trains, and blindsight. Plus, we'll test your knowledge of some recent science in the news