Podcasts about pluripotent stem cell

Sometimes experimental results are serendipitous. Listen as Associate Editor Dr. Crystal Ripplinger (University of California, Davis) talks with authors Dr. Nikki Posnack and Devon Guerrelli (both at Children's National Hospital and The George Washington University School of Engineering and Applied Science), along with expert Dr. Silvia Marchiano (University of Washington), about the new research by Guerrelli et al. published in our Call for Papers on Excitation-Contraction Coupling, Electrophysiology, and Arrhythmias. The Posnack Lab typically investigates environmental chemicals and their impact on cardiac function using microelectrode arrays to record electrical signals from human iPS cells. When performing cardiotoxicity experiments, the authors realized that their baseline measurements varied significantly between their different studies, making it difficult to combine datasets. In doing the legwork to identify potential sources of variability and improve their own internal lab protocols, the authors focused on the reproducibility of their experimental measurements using human iPSCs. Listen as we discuss important recommendations for investigators using these cells to improve their experimental reproducibility.   Devon Guerrelli, Jenna Pressman, Shatha Salameh, and Nikki Posnack hiPSC-CM Electrophysiology: Impact of Temporal Changes and Study Parameters on Experimental Reproducibility Am J Physiol Heart Circ Physiol, published June 9, 2024. DOI: 10.1152/ajpheart.00631.2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551225v1?rss=1 Authors: Baert, L., Rudy, S., Pellisson, M., Doll, T., Rocchetti, R., Kaiser, M., Mäser, P., Müller, M. Abstract: The parasite Leishmania donovani is one of the species causing visceral leishmaniasis in humans, a deadly infection claiming up to 40,000 lives each year. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifestyle of Leishmania. Here, we investigate the use of human induced pluripotent stem cell (iPS)-derived macrophages (iMACs) as host cells for L. donovani. iMACs obtained through embryoid body differentiation were infected with L. donovani promastigotes, and high-content imaging techniques were used to optimise the iMACs seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50 values obtained for miltefosine and amphotericin B using the infected iMACs or mouse peritoneal macrophages as host cells were comparable and in agreement with the literature, showing the potential of iMACs as an infection model for drug screening. 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/2023.07.29.551071v1?rss=1 Authors: Bartke, R., Hockemeyer, D. Abstract: Telomeric DNA ends in a 3' single stranded overhang that is implicated in the protective function of telomeres ensuring genomic stability in mammals. Telomere overhang formation relies on the coordinated interplay between DNA synthesis and exonuclease activity. DCLRE1B/hSNM1B/Apollo generates an initial resection at the newly synthesized, blunt-ended leading strand telomere. This resection is thought to be required for further nucleolytic processing at the leading strand telomere. Here, we investigated the functional relevance of Apollo in human pluripotent stem cells (hPSCs) by generating Apollo deficient cells. Leveraging CRISPR/Cas9 technology, we generated locally haploid hPSCs (loHAPs) that lack one allele of Apollo. Subsequently, we mutated the remaining Apollo allele and monitored the resultant allele spectrum over 3 weeks. Surprisingly, cells survived regardless of Apollo status. These results suggest that, in hPSCs, Apollo is not acutely essential for cellular survival. 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/2023.07.21.550059v1?rss=1 Authors: Muhammad, Z., Brown, P. W., Babazau, L., Alkhamis, A. I., Goni, B. W., Nggada, H. A., Mbaya, K. M., Wray, S., Marte, I. H., Karch, C., Serpell, L., Maina, M. B. Abstract: Genetic backgrounds contribute to cellular phenotypes, drug responsiveness, and health outcomes. However, the majority of human induced pluripotent stem cell (iPSC) lines are derived from individuals of European descent. Thus, there is a major, unmet need in the generation, characterisation, and distribution of iPSCs from diverse ancestries. To begin to address this need, we have generated iPSCs from dermal fibroblasts isolated from a healthy 60-year-old indigenous Nigerian male belonging to the Babur ethnic group. The iPSCs were generated using Sendai virus, and copy number variation (CNV) analysis revealed no new major abnormalities compared to the parental fibroblasts. The iPSCs have been characterised for pluripotency markers and morphology and successfully differentiated into neural progenitor cells and astrocytes. This iPSC line could serve as a healthy control in comparative studies and can be used in disease modelling, toxicity assessments, genetic analyses, and drug discovery processes within an African genetic background. To bolster the inclusion of African models in biomedical research, this iPSC line will be made available to the broader scientific community. Ongoing efforts focus on generating more lines from diverse indigenous populations towards creating a dedicated open-access African iPSC biobank. 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/2023.07.12.548684v1?rss=1 Authors: Pranty, A. I., Wruck, W., Adjaye, J. Abstract: Bilirubin induced neurological damage (BIND), which is also known as Kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus resulting in unconjugated bilirubin (UCB) to cross the blood brain barrier (BBB) and accumulation. Severe hyperbilirubinemia can be caused by a mutation within the UGT1A1 encoding gene. This mutation has a direct contribution towards bilirubin conjugation leading to Kernicterus as a symptom of Crigler Najjar Syndromes (CNS1, CNS2) and Gilbert syndrome, which results in permanent neurological sequelae. In this comparative study, we used human induced pluripotent stem cells (hiPSCs) derived 3D-brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of UCB in the developing human brain. hiPSC derived from healthy and CNS patients were differentiated into day 20 brain organoids, these were then stimulated with 200nM UCB. Analyses at 24 and 72 hrs post-treatment point at UCB induced neuro-inflammation in both cell lines. Transcriptome and associated KEGG and Gene Ontology analyses unveiled activation of distinct inflammatory pathways such as cytokine cytokine receptor interaction, MAPK signaling, calcium signaling, NFkB activation. Furthermore, both mRNA expression and secretome analysis confirmed an upregulation of proinflammatory cytokines such as IL6 and IL8 upon UCB stimulation. In summary, this novel study has provided insights into how a human iPSC derived 3D-brain organoid model can serve as a prospective platform for studying the etiology of BIND Kernicterus. 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/2023.06.26.546577v1?rss=1 Authors: Bosworth, A., Griffin, C., Chakhoyan, A., Sagare, A. P., Nelson, A. R., Wang, Y., Kisler, K., Montagne, A., Clementel, V., TCW, J., Rust, R., Coba, M., Zlokovic, B. Abstract: Brain pericytes maintain blood-brain barrier (BBB), secrete neurotrophic factors and clear toxic proteins. Their loss in neurological disorders leads to BBB breakdown, neuronal dysfunction, and cognitive decline. Therefore, cell therapy to replace lost pericytes holds potential to restore impaired cerebrovascular and brain functions. Here, we show by a quantitative analysis of 8,344 proteins and 20,572 phosphopeptides that human iPSC-derived brain pericytes (iPSC-PC) share 96% of total proteins and 98% of protein phosphorylation sites with primary human brain pericytes. This includes cell adhesion and tight junction proteins, transcription factors, and different protein kinase families of the human kinome. In pericyte-deficient mice, iPSC-PC home to host brain capillaries to form hybrid human-mouse microvessels. They repair BBB leaks and protect against neuron loss, which we show requires PDGRFB and pleiotrophin. They also clear Alzheimer's amyloid-{beta} and tau neurotoxins via lipoprotein receptor. Thus, iPSC-PC may offer a valuable replacement therapy for pericyte-deficient neurological disorders. 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/2023.04.26.538393v1?rss=1 Authors: Zhang, W., Zhao, X., Qi, X., Kimber, S. J., Hooper, N., Wang, T. Abstract: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common genetic small vessel disease caused by variants in the NOTCH3 gene. Patients with CADASIL experience recurrent strokes, developing into cognitive defect and vascular dementia. CADASIL is a late-onset vascular condition, but migraine and brain MRI lesions appear in CADASIL patients as early as their teens and twenties, suggesting an abnormal neurovascular interaction at the neurovascular unit (NVU) where microvessels meet the brain parenchyma. To understand the molecular mechanisms of CADASIL, we established induced pluripotent stem cell (iPSC) models from CADASIL patients and differentiated the iPSCs into the major NVU cell types including brain microvascular endothelial-like cells (BMECs), vascular mural cells (MCs), astrocytes and cortical projection neurons. We then built an in vitro NVU model by co-culturing different neurovascular cell types in Transwells and evaluated the blood brain barrier (BBB) function by measuring transendothelial electrical resistance (TEER). Results showed that, while the wild-type MCs, astrocytes and neurons could all independently and significantly enhance TEER values of the iPSC-BMECs, such capability of MCs from iPSCs of CADASIL patients was significantly impeded. Additionally, the barrier function of the BMECs from CADASIL iPSCs was significantly impaired, accompanied with disorganised tight junctions in iPSC-BMECs, which could not be effectively rescued by the wild-type MCs, astrocytes and neurons. Our findings provide new insight into early disease pathologies on the neurovascular interaction and BBB function at the molecular and cellular levels for CADASIL, which helps inform future therapeutic development. 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/2023.03.20.533543v1?rss=1 Authors: Ragunton, B. L., Van Buskirk, S., Wakefield, D., Randive, N., Pipathsouk, A., Pei, B., Zhou, H., Yamawaki, T. M., Berke, M., Li, C.-M. K., Hale, C., Wang, S., Chambers, S. Abstract: The current state-of-the-art in hPSC culture is a bespoke and user-dependent process limiting the scale and complexity of the experiments performed and introducing operator-to-operator and day-to-day variation. Artificial intelligence (AI) offers the speed and flexibility to bridge the gap between a human-dependent process and industrial-scale automation. We evaluated an AI approach for counting exact cell numbers of undifferentiated human induced pluripotent stem cells in brightfield images for automating hPSC culture. The neural network generates a topological density map for accurate cell counts. We found that the imagebased AI algorithm can determine a precise number of hPSCs and is superior to fluorescencelabeled object detection; the algorithm can ignore well edges, meniscus effects, and dust, achieving an average error of 5.6%. We have built a prototype capable of making a go/no go decision for stem cell passaging to perform 26,400 individual well-level counts from 422,400 images in 12 hours at low cost. 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/2023.02.21.529337v1?rss=1 Authors: Akiyama, S., Saku, N., Miyata, S., Ite, K., Nonaka, H., Toyoda, M., Kamiya, A., Kiyono, T., Kimura, T., Kasahara, M., Umezawa, A. Abstract: As a metabolic organ, the liver plays a variety of roles, including detoxification. It has been difficult to obtain stable supplies of hepatocytes for transplantation and for accurate hepatotoxicity determination in drug discovery research. Human pluripotent stem cells, capable of unlimited self-renewal, may be a promising source of hepatocytes. In order to develop a stable supply of embryonic stem cell (ESC)-derived hepatocytes, we have purified human ESC-derived hepatic progenitor cells with exposure to cytocidal puromycin by using their ability to metabolize drugs. Hepatic progenitor cells stably proliferated at least 2^20-fold over 120 days, maintaining hepatic progenitor cell-like properties. High drug-metabolizing hepatic progenitor cells can be matured into liver cells by suppressing hepatic proliferative signals. The method we developed enables the isolation and proliferation of functional hepatic progenitors from human ESCs, thereby providing a stable supply of high-quality cell resources at high efficiency. Cells produced by this method may facilitate cell therapy for hepatic diseases and reliable drug discovery research. 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/2023.01.11.523290v1?rss=1 Authors: Mazzarino, R. C., Perez-Corredor, P. A., Vanderleest, T. E., Vacano, G. N., Sanchez, J., Villalba-Moreno, N. D., Krasemann, S., Mendivil Perez, M. A., Aguillon, D., Jimenez-Del-Rio, M., Baena, A., Sepulveda-Falla, D., Lopera-Restrepo, F., Quiroz-Gaviria, Y., Arboleda-Velasquez, J. F. Abstract: Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated {beta}-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's. 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/2022.10.28.513298v1?rss=1 Authors: Nguyen Ngoc, K. V., Sai, S., Jun, Y., Bender, R. H. F., Kravets, V., Zhu, H., Hatch, C. J., Schlichting, M., Gaetani, R., Mallick, M., Hachey, S. J., Christman, K., George, S. C., Hughes, C. C., Sander, M. Abstract: Blood vessels play a critical role in pancreatic islet health and function, yet current culture methods to generate islet organoids from human pluripotent stem cells (SC-islets) lack a vascular component. Here, we engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts both in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+ influx into SC-{beta}-cells, a hallmark of {beta}-cell function that is blunted in non-vascularized SC-islets. We show that an islet-like basement membrane is formed by vasculature and contributes to the functional improvement of SC-{beta}-cells. Furthermore, cell-cell communication networks based on scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-{beta}-cells. Correspondingly, BMP4 augmented the SC-{beta}-cell Ca2+ response and insulin secretion. These vascularized SC-islet models will enable further studies of crosstalk between {beta}-cells and ECs and can serve as in vivo-mimicking platforms for disease modeling and therapeutic testing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Thorold Theunissen, Ph.D., of the Washington University School of Medicine in St. Louis shares his work using naive stem cells to model trophoblast development, Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37674]

Kleanthis Xanthopoulos is Co-Founder and CEO of Shoreline Biosciences. He talks about the Shoreline cell therapy platform that uses standardized manufacturing of allogeneic induced pluripotent stem cells to create an effective treatment to kill tumor cells with multiple advantages over autologous T-cell therapies. Kleanthis explains, "We are focusing specifically on two different effector cells, Natural Killers and Macrophages, and we derive them from a platform which is induced pluripotent stem cells. This gives us the ability to really engineer the NK cells and Macrophages that we derive from iPSC, so they become allogeneic standardized, meaning they can be introduced to any patient and then are targeted and specific." "Initial clinical results are showing us that iPSC derived NK cells don't appear to have the kind of side effects that you see with T-cells. So we are very, very excited about that. And we are seeing that there's a different dimension in cell therapies that can be served very, very nicely through these allogeneic pluripotent stem cell based therapies." After the interview, Shoreline announced it has raised $140 million in its latest fundraising round. #ShorelineBio #ShoreBiosciences #Oncology #Immunotherapy #NKCells #iPSC #Macrophages #SanDiego Shorelinebio.com Download the transcript here  

Kleanthis Xanthopoulos is Co-Founder and CEO of Shoreline Biosciences. He talks about the Shoreline cell therapy platform that uses standardized manufacturing of allogeneic induced pluripotent stem cells to create an effective treatment to kill tumor cells with multiple advantages over autologous T-cell therapies. Kleanthis explains, "We are focusing specifically on two different effector cells, Natural Killers and Macrophages, and we derive them from a platform which is induced pluripotent stem cells. This gives us the ability to really engineer the NK cells and Macrophages that we derive from iPSC, so they become allogeneic standardized, meaning they can be introduced to any patient and then are targeted and specific." "Initial clinical results are showing us that iPSC derived NK cells don't appear to have the kind of side effects that you see with T-cells. So we are very, very excited about that. And we are seeing that there's a different dimension in cell therapies that can be served very, very nicely through these allogeneic pluripotent stem cell based therapies." After the interview, Shoreline announced it has raised $140 million in its latest fundraising round. #ShorelineBio #ShoreBiosciences #Oncology #Immunotherapy #NKCells #iPSC #Macrophages #SanDiego Shorelinebio.com Listen to the podcast here  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.09.331710v1?rss=1 Authors: Xu, R., Boreland, A. J., Li, X., Erickson, C., Jin, M., Atkins, C., Pang, Z., Daniels, B. P., Jiang, P. Abstract: Microglia, as the brain-resident macrophages, play critical roles in brain development, homeostasis, and disease. Microglia in animal models cannot accurately model the properties of human microglia, because there are due to notable transcriptomic and functional differences between human and other animal microglia at transcriptomic and functional levels. Efficient generation of microglia from human pluripotent stem cells (hPSCs) provides unprecedented opportunities to study the function and behavior of human microglia. Particularly, incorporating hPSCs-derived microglia into brain organoids facilitates their development in a 3-dimensional context, mimicking the brain environment. However, an optimized method that integrates an appropriate amount of microglia into brain organoids at a proper time point, similar to what is seen in vivo, is still needed. Here, we report the development of a new brain region-specific, microglia-containing organoid model by co-culturing hPSCs-derived primitive neural progenitor cells (pNPCs) and primitive macrophage progenitors (PMPs). In these organoids, hPSCs-derived pNPCs and PMPs interact with each other and develop into functional neurons, astroglia, and microglia, respectively. Importantly, the numbers of human microglia population in the organoids can be controlled, resulting in a cell type at a ratio similar to that seen in the human brain. Importantly, uUsing super-resolution microscopy, we demonstrate that these human microglia are able to phagocytize neural progenitor cells (NPCs) and dead cells, as well as to prune synapses at different developmental stages of the organoids. Furthermore, these human microglia respond to Zika virus infection in of the organoids, as indicated by exhibiting amoeboid-like morphology, an increased expression of gene transcripts encoding inflammatory cytokines, and excessive pruning of synaptic materials. ThusTogether, our findings establish a new microglia-containing brain organoid model that will serve to study human microglial function in a variety of neurological disorders. Copy rights belong to original authors. Visit the link for more info

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Mark Mercola, PhD Stanford University Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 36334]

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.22.308726v1?rss=1 Authors: Zerti, D., Hilgen, G., Dorgau, B., Collin, J., Ader, M., Armstrong, L., Sernagor, E., Lako, M. Abstract: Retinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Up to 1.5% of precursors integrated into the host retina, differentiated into cones and formed synapses with bipolar cells. Half of the transplanted mice exhibited visual behaviour and 33% showed binocular light sensitivity. The majority of ganglion cells exhibited contrast-sensitive ON, OFF or ON-OFF light responses and even motion sensitivity. Many cells also exhibited unusual responses (e.g. light-induced suppression), presumably reflecting remodelling of the neural retina. Our data indicate that despite relatively low engraftment yield, engrafted pluripotent stem cell-derived cone precursors can elicit light responsiveness even at advanced degeneration stages. Further work is needed to improve engraftment yield and counteract retinal remodelling to achieve useful clinical applications. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.28.225151v1?rss=1 Authors: Jacob, F., Pather, S., Huang, W.-K., Wong, S. Z. H., Zhou, H., Zhang, F., Cubitt, B., Chen, C. Z., Xu, M., Pradhan, M., Zhang, D. Y., Zheng, W., Bang, A. G., Song, H., de la Torre, J. C., Ming, G.-l. Abstract: Neurological complications are common in patients with COVID-19. While SARS-CoV-2, the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function are not well understood, and experimental models using human brain cells are urgently needed. Here we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found modest numbers of infected neurons and astrocytes, but greater infection of choroid plexus epithelial cells. We optimized a protocol to generate choroid plexus organoids from hiPSCs, which revealed productive SARS-CoV-2 infection that leads to increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our results provide evidence for SARS-CoV-2 neurotropism and support use of hiPSC-derived brain organoids as a platform to investigate the cellular susceptibility, disease mechanisms, and treatment strategies for SARS-CoV-2 infection. Copy rights belong to original authors. Visit the link for more info

The words “induced pluripotent stem cell” refer to a group of cells that are gathered from a person with a disorder, like autism, then changed or “induced” from a skin cell into an embryonic “stem” cell, and can be then made into baby brain cells, or baby heart cells or baby bone cells. This makes […]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Tony Wynshaw-Boris, MD, PhD describes his lab's efforts to use mouse and IPSC models to find commonalities that give insight into the complex disorder of autism. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34977]

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

April Pyle, Department of Microbiology, Immunology and Molecular Genetics at UCLA, uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. She studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy. Series: "Women in Science" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34442]

April Pyle, Department of Microbiology, Immunology and Molecular Genetics at UCLA, uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. She studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy. Series: "Women in Science" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34442]

April Pyle, Department of Microbiology, Immunology and Molecular Genetics at UCLA, uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. She studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy. Series: "Women in Science" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34442]

April Pyle, Department of Microbiology, Immunology and Molecular Genetics at UCLA, uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. She studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy. Series: "Women in Science" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34442]

April Pyle, Department of Microbiology, Immunology and Molecular Genetics at UCLA, uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. She studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy. Series: "Women in Science" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34442]

April Pyle, Department of Microbiology, Immunology and Molecular Genetics at UCLA, uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. She studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy. Series: "Women in Science" [Health and Medicine] [Science] [Education] [Professional Medical Education] [Show ID: 34442]

People with autism have difficulty with language and social interaction as if they are trapped inside their own brains. There is no cure. Dr. Alysson Muotri of UCSD devised a Fairy Tooth Kit Collection campaign in which autistic and unaffected kids could donate their baby teeth when they fell out. Using the induced pluripotent stem cell (iPS) technique, Muotri's team extracted pulp cells in the teeth and converted them into brain cells. The autistic brain cells showed distinct deficiencies in the petri dish which could be reversed. In this seminar presented to the governing Board of California's Stem Cell Agency, Dr. Muotri describes these results in more detail. Series: "Stem Cell Channel" [Health and Medicine] [Show ID: 28241]

People with autism have difficulty with language and social interaction as if they are trapped inside their own brains. There is no cure. Dr. Alysson Muotri of UCSD devised a Fairy Tooth Kit Collection campaign in which autistic and unaffected kids could donate their baby teeth when they fell out. Using the induced pluripotent stem cell (iPS) technique, Muotri's team extracted pulp cells in the teeth and converted them into brain cells. The autistic brain cells showed distinct deficiencies in the petri dish which could be reversed. In this seminar presented to the governing Board of California's Stem Cell Agency, Dr. Muotri describes these results in more detail. Series: "Stem Cell Channel" [Health and Medicine] [Show ID: 28241]

Robert Passier, Leiden University Medical Center LUMC, Leiden – THE NETHERLANDS, speaks on "Human pluripotent stem cell-derived cardiomyocytes for regenerative medicine" . This seminar has been recorded by ICGEB

Guest: Ken Aldrich Host: Bruce Japsen Expanded guidelines for stem cell research have favored federal financing for embryonic stem cell development. But some researchers in the field are looking beyond embryonic stem cells. Ken Aldrich, chief executive officer and co-founder of International Stem Cell Corporation, tells host Bruce Japsen about pluripotent stem cell research, not yet eligible for federal funding.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.10.036400v1?rss=1 Authors: Swartz, E. W., Shintani, G., Wan, J., Maffei, J. S., Wang, S. H., Miller, B. L., Havton, L. A., Coppola, G. Abstract: The failure of the neuromuscular junction (NMJ) is a key component of degenerative neuromuscular disease, yet how NMJs degenerate in disease is unclear. Human induced pluripotent stem cells (hiPSCs) offer the ability to model disease via differentiation toward affected cell types, however, the re-creation of an in vitro neuromuscular system has proven challenging. Here we present a scalable, all-hiPSC-derived co-culture system composed of independently derived spinal motor neurons (MNs) and skeletal myotubes (sKM). In a model of C9orf72-associated disease, co-cultures form functional NMJs that can be manipulated through optical stimulation, eliciting muscle contraction and measurable calcium flux in innervated sKM. Furthermore, co-cultures grown on multi-electrode arrays (MEAs) permit the pharmacological interrogation of neuromuscular physiology. Utilization of this co-culture model as a tunable, patient-derived system may offer significant insights into NMJ formation, maturation, repair, or pathogenic mechanisms that underlie NMJ dysfunction in disease. Copy rights belong to original authors. Visit the link for more info