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Stem Cells

Mitch Biermann, Wenxuan Cai, Di Lang, Jack Hermsen, Luke Profio, Ying Zhou, Andras Czirok, Dona G Isai, Brett N Napiwocki, Adriana M Rodriguez, Matthew E Brown, Marites T Woon, Annie Shao, Tianxiao Han, Donglim Park, Timothy A Hacker, Wendy C Crone, William J Burlingham, Alexey V Glukhov, Ying Ge, Timothy J Kamp
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs...
May 14, 2019: Stem Cells
James Spyrou, David K Gardner, Alexandra J Harvey
The transition to pluripotency invokes profound metabolic restructuring, however reprogramming is accompanied by the retention of somatic cell metabolic and epigenetic memory. Modulation of metabolism during reprogramming has been shown to improve reprogramming efficiency, yet it is not known how metabolite availability during reprogramming affects the physiology of resultant induced pluripotent stem cells (iPSC). Metabolic analyses of iPSC generated under either physiological (5%; P-iPSC) or atmospheric (20%; A-iPSC) oxygen conditions revealed they retained aspects of somatic cell metabolic memory and failed to regulate carbohydrate metabolism, with A-iPSC acquiring different metabolic characteristics...
May 1, 2019: Stem Cells
Xiaoyu Zhang, Rui Wei, Yizhuo Sun, Qin Xia, Wenhai Xie, Hongfei Song, Wei Wang, Kang Zou
Female germline stem cells (FGSCs) are the rare population residing in cortex of ovary, with the potential to rescue female infertility caused by ovary failure. Recently, we reported that Cadherin-22 (CDH22), a member of cadherin family, regulates self-renewal of mouse FGSCs via interaction with JAK-STAT signal pathway and β-catenin. In this study, the expression profiles of FGSCs and spermatogonial stem cells (SSCs) were analyzed to further reveal their similarity and difference, and AKT3 was predicted as a pivotal molecule for FGSCs self-renewal...
May 1, 2019: Stem Cells
Raghavan Chinnadurai, Jenna Sands, Devi Rajan, Xiao Liu, Dalia Arafat, Rahul Das, Frank A Anania, Greg Gibson, Tatiana Kisseleva, Jacques Galipeau
Defining the immune physiology of culture-adapted Mesenchymal stromal Cells (MSCs) derived from distinct tissue compartments informs their potential utility as pharmaceuticals. Here we have investigated the comparative immune plasticity of MSCs and Hepatic Stellate Cells (HeSCs) isolated from human and murine bone marrow and liver respectively. Although both bone marrow MSCs (BM-MSCs) and HeSCs share mesenchymal phenotype and overall molecular genetic responses to inflammatory cues, HeSCs differ from BM-MSCs in a meaningful manner...
April 29, 2019: Stem Cells
Jun Fujita, Shugo Tohyama, Yoshikazu Kishino, Marina Okada, Yuika Morita
Human pluripotent stem cells (hPSCs; including both embryonic stem cells and induced pluripotent stem cells) are the ideal cell sources for disease modeling, drug discovery, and regenerative medicine. In particular, regenerative therapy with hPSC-derived cardiomyocytes (CMs) is an unmet medical need for the treatment of severe heart failure. Cardiac differentiation protocols from hPSCs are made on the basis of cardiac development in vivo. However, current protocols have yet to yield 100% pure cardiomyocytes and their maturity is low...
April 25, 2019: Stem Cells
Carlos Godoy-Parejo, Chunhao Deng, Weiwei Liu, Guokai Chen
Insulin is present in most maintenance media for human embryonic stem cells, but little is known approximately its essential role in the cell survival of individualized cells during passage. In this report, we show that insulin suppresses caspase cleavage and apoptosis after dissociation. Insulin activates IGF receptor and PI3K/AKT cascade to promote cell survival, and its function is independent of ROCK kinase regulation. During niche reformation after passaging, insulin activates integrin that is essential for cell survival...
April 25, 2019: Stem Cells
Evgeny I Bakhmet, Igor B Nazarov, Adel R Gazizova, Nadezhda E Vorobyeva, Andrey A Kuzmin, Mikhail N Gordeev, Sergey A Sinenko, Nikolai D Aksenov, Tatyana O Artamonova, Mikhail A Khodorkovskii, Natalia Alenina, Daria Onichtchouk, Guangming Wu, Hans R Schöler, Alexey N Tomilin
The transcription factor Oct4 plays a key regulatory role in the induction and maintenance of cellular pluripotency. With this paper, we show that ubiquitous and multifunctional poly(C) DNA/RNA-binding protein hnRNP-K occupies Oct4 (Pou5f1) enhancers in embryonic stem cells (ESCs) but is dispensable for the initiation, maintenance, and downregulation of Oct4 gene expression. Nevertheless, hnRNP-K has an essential cell-autonomous function in ESCs to maintain their proliferation and viability. To better understand mechanisms of hnRNP-K action in ESCs we have performed ChIP-seq analysis of genome-wide binding of hnRNP-K and identified several thousands of hnRNP-K target sites that are frequently co-occupied by pluripotency-related and common factors (Oct4, TBP, Sox2, Nanog, Otx2, etc...
April 25, 2019: Stem Cells
Jung-Hyun Kim, Alex Alderton, Nissim Benvenisty, Catharina Brandsten, Meri Firpo, Peter W Harrison, Shin Kawamata, Eihachiro Kawase, Andreas Kurtz, Jeanne F Loring, Tenneille Ludwig, Jennifer Man, Joanne C Mountford, Marc L Turner, Steve Oh, Lygia da Veiga Pereira, Patricia Pranke, Micheal Sheldon, Rachel Steeg, Stephen Sullivan, Michael Yaffe, Qi Zhou, Glyn N Stacey
This report summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at Harvard Stem Cell Institute, Boston, USA, on 18th Jun 2017. In this meeting, we aimed to find consensus on ongoing issues of quality control (QC), safety and efficacy of human pluripotent stem cell (hPSC) banks and their derivative cell therapy products for the global harmonization. In particular, assays for the QC testing such as pluripotency assays test and general QC testing criteria was intensively discussed...
April 25, 2019: Stem Cells
Ritu Kumar, Todd Evans
Induced pluripotent stem cells (iPSCs) derived by in vitro reprogramming of somatic cells retain the capacity to self-renew and to differentiate into many cell types. Pluripotency encompasses multiple states, with naïve iPSCs considered as ground state, possessing high levels of self-renewal capacity and maximum potential without lineage restriction. We showed previously that activation-induced cytidine deaminase (AICDA), facilitates stabilization of pluripotency during reprogramming. Here we report that Acida-/- iPSCs, even when successfully reprogrammed, fail to achieve the naïve pluripotent state, and remain primed for differentiation, because of a failure to suppress FGF/ERK signaling...
April 25, 2019: Stem Cells
Seppe Vander Beken, Juliane C de Vries, Barbara Meier-Schiesser, Patrick Meyer, Dongsheng Jiang, Anca Sindrilaru, Filipa F Ferreira, Adelheid Hainzl, Susanne Schatz, Jana Muschhammer, Natalie J Scheurmann, Panagiotis Kampilafkos, Andreas M Seitz, Lutz Dürselen, Anita Ignatius, Mark A Kluth, Christoph Ganss, Meinhard Wlaschek, Karmveer Singh, Pallab Maity, Natasha Y Frank, Markus H Frank, Karin Scharffetter-Kochanek
Here we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of non-healing wounds. Local administration of dermal ABCB5+ -derived MSCs attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron overload mouse model mimicking the non-healing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+ -derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained pro-inflammatory M1 macrophages toward repair promoting anti-inflammatory M2 macrophages at the wound site...
April 19, 2019: Stem Cells
Anna Andrzejewska, Barbara Lukomska, Miroslaw Janowski
It was shown as long as half a century ago that bone marrow is a source of not only hematopoietic stem cells, but also stem cells of mesenchymal tissues. Then the term of mesenchymal stem cells (MSCs) has been coined in early 1990s and over a decade later the criteria for defining MSCs have been released by International Society for Cellular Therapy. The easy derivation from a variety of fetal and adult tissues and not demanding cell culture conditions made MSCs an attractive research object. It was followed by the avalanche of reports from preclinical studies on potentially therapeutic properties of MSCs such as immunomodulation, trophic support and capability for a spontaneous differentiation into connective tissue cells, and differentiation into majority of cell types upon specific inductive conditions...
April 12, 2019: Stem Cells
Wei Guo, Henk Roelink
As a morphogen, Sonic Hedgehog (Shh) mediates signaling at a distance from its sites of synthesis. After secretion, Shh must traverse a distance through the extracellular matrix (ECM) to reach the target cells and activate the Hh response. Extracellular matrix proteins, in particular the heparan sulfate proteoglycans (HSPGs) of the glypican family have both negative and positive effects on Shh signaling, all attributed to their ability to bind Shh. Using mouse embryonic stem cell-derived mosaic tissues with compartments that lack the glycosyltransferases Exostosin1 (Ext1) and Exostosin2 (Ext2), or the HSPG core protein Glypican5, we show that Shh accumulates around its source cells when they are surrounded by cells that have a mutated extracellular matrix...
April 12, 2019: Stem Cells
Xue Li, Limei Wu, Morgan Zopp, Shaina Kopelov, Wei Du
Emerging evidence have shown that resting quiescent hematopoietic stem cells (HSCs) prefer to utilize anaerobic glycolysis rather than mitochondrial respiration for energy production. Compelling evidence has also revealed that altered metabolic energetics in HSC underlies the onset of certain blood diseases. However, the mechanisms responsible for energetic reprogramming remain elusive. We recently found that Fanconi anemia (FA) HSCs are more dependent on mitochondrial respiration relative to glycolysis in their resting state for energy metabolism...
April 12, 2019: Stem Cells
Xavier Leveque, Mazene Hochane, Fanny Geraldo, Solene Dumont, Catherine Gratas, Lisa Oliver, Claire Gaignier, Valérie Trichet, Pierre Layrolle, Dominique Heymann, Olivier Herault, François M Vallette, Christophe Olivier
The general population is chronically exposed to multiple environmental contaminants such as pesticides. We have previously demonstrated that human mesenchymal stem cells (MSC) exposed in vitro to low doses of a mixture of seven common pesticides showed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation toward adipogenesis. We thus hypothesized that common combination of pesticides may induce a premature cellular aging of adult MSC...
April 12, 2019: Stem Cells
Barbara Romano, Sudharshan Elangovan, Marco Erreni, Sala Emanuela, Luciana Petti, Paolo Kunderfranco, Luca Massimino, Silvia Restelli, Shruti Sinha, Donatella Lucchetti, Achille Anselmo, Federico Simone Colombo, Matteo Stravalaci, Vincenzo Arena, Silvia D'Alessio, Federica Ungaro, Antonio Inforzato, Angelo A Izzo, Alessandro Sgambato, Anthony J Day, Stefania Vetrano
Mesenchymal stem cells (MSCs) are largely studied for their promising therapeutic properties. TSG-6, a potent tissue-protective and anti-inflammatory factor, has been demonstrated to be responsible for a significant part of wound healing-promoting properties mediated by MSCs. Nevertheless, current knowledge approximately the biological function of TSG-6 in MSCs is limited. Here, we demonstrated that TSG-6 is a crucial factor that influences many functional properties of MSCs. The transcriptomic sequencing analysis of WT and TSG-6-/- -MSCs shows that the loss of TSG-6 leads to the perturbation of several transcription factors, cytokines and other pathways involved in MSCs biological processes...
April 3, 2019: Stem Cells
Yan Du, Hongwei Shao, Mecker Moller, Rochelle Prokupets, Yee Ting Tse, Zhao-Jun Liu
Cancer stem cells (CSCs) play critical roles in cancer initiation, metastasis, recurrence and drug resistance. Recent studies have revealed involvement of cancer-associated fibroblasts (CAF) in regulating CSCs. However, the intracellular molecular mechanisms that determine the regulatory role of CAF in modulating the plasticity of CSCs remain unknown. Here, we uncovered that intracellular Notch1 signaling in CAF serves as a molecular switch, which modulates tumor heterogeneity and aggressiveness by inversely controlling stromal regulation of the plasticity and stemness of CSCs...
April 2, 2019: Stem Cells
Tatsuhiro Sakamoto, Naoshi Obara, Hidekazu Nishikii, Takayasu Kato, Cao Sy Luan, Ryosuke Fujimura, Hideo Yagita, Mamiko Sakata-Yanagimoto, Satoru Takahashi, Shigeru Chiba
Notch signaling plays pivotal roles in both hematopoietic stem/progenitor and their niche cells. Myeloproliferative phenotypes are induced by disruption of Notch signaling in non-hematopoietic bone marrow (BM) cells. Nestin-expressing cells in the BM reportedly represent a component of the hematopoietic stem cell niche. We established mice in which rare Nestin-expressing cells in the BM were marked by green fluorescent protein and Notch signaling was conditionally disrupted in these cells specifically. We observed impairment of erythropoiesis in the BM accompanying splenomegaly with BM hematopoietic programs in other lineages undisturbed...
April 1, 2019: Stem Cells
Jason S L Yu, Giorgia Palano, Cindy Lim, Aldo Moggio, Lauren Drowley, Alleyn T Plowright, Mohammad Bohlooly-Y, Barry S Rosen, Emil M Hansson, Qing-Dong Wang, Kosuke Yusa
Direct in vivo reprogramming of cardiac fibroblasts (CF) into myocytes is an attractive therapeutic intervention in resolving myogenic deterioration. Current transgene-dependent approaches can restore cardiac function, but dependence on retroviral delivery and persistent retention of transgenic sequences are significant therapeutic hurdles. Chemical reprogramming has been established as a legitimate method to generate functional cell types including those of the cardiac lineage. Here, we have extended this approach to generate progenitor cells that can differentiate into endothelial cells (EC) and cardiomyocytes (CM) using a single inhibitor protocol...
April 1, 2019: Stem Cells
Aurélie Soubéran, Jessica Cappaï, Mathieu Chocry, Christopher Nuccio, Julie Raujol, Carole Colin, Daniel Lafitte, Hervé Kovacic, Véronique Quillien, Nathalie Baeza-Kallee, Geneviève Rougon, Dominique Figarella-Branger, Aurélie Tchoghandjian
In glioblastomas, apoptosis inhibitor proteins (IAPs) are involved in apoptotic and non-apoptotic processes. We previously showed that IAPs inhibition induced a loss of stemness and glioblastoma stem cells differentiation by activating nuclear factor-κB under normoxic conditions. Hypoxia has been shown to modulate drug efficacy. Here, we investigated how IAPs participate in glioblastoma stem-like cell maintenance and fate under hypoxia. We showed that in a hypoxic environment, IAPs inhibition by GDC-0152, a small-molecule IAPs inhibitor, triggered stem-like cell apoptosis and decreased proliferation in four human glioblastoma cell lines...
March 28, 2019: Stem Cells
Jialiang Liang, Wei Huang, Lin Jiang, Christian Paul, Xiangnan Li, Yigang Wang
Pluripotent stem cells (PSCs) are an attractive, reliable source for generating functional cardiomyocytes for regeneration of infarcted heart. However, inefficient cell engraftment into host tissue remains a notable challenge to therapeutic success due to mechanical damage or relatively inhospitable microenvironment. Evidence has shown that excessively formed scar tissues around cell delivery sites present as mechanical and biological barriers that inhibit migration and engraftment of implanted cells. In this review, we focus on the functional responses of stem cells and cardiomyocytes during the process of cardiac fibrosis and scar formation...
March 26, 2019: Stem Cells
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