Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy
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TLDR
The potential paracrine mechanisms involved in adult stem cell signaling and therapy are reviewed: cytokines and growth factors can induce cytoprotection and neovascularization, and cardiac remodeling, contractility, and metabolism may also be influenced in aParacrine fashion.Abstract:
Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.read more
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Growth Factors, Matrices, and Forces Combine and Control Stem Cells
TL;DR: Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.
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Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6
Ryang Hwa Lee,Andrey A. Pulin,Min Jeong Seo,Daniel J. Kota,Daniel J. Kota,Joni Ylostalo,Joni Ylostalo,Benjamin L. Larson,Benjamin L. Larson,Laura Semprun-Prieto,Patrice Delafontaine,Darwin J. Prockop,Darwin J. Prockop +12 more
TL;DR: Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment and suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of M SCs to secrete TSG-6.
Journal ArticleDOI
Exosomes/microvesicles as a mechanism of cell-to-cell communication
TL;DR: The transfer of gene products from injured cells may explain stem cell functional and phenotypic changes without the need of transdifferentiation into tissue cells, and the evidence supporting a bidirectional exchange of genetic information between stem and injured cells is discussed.
Journal ArticleDOI
Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury
Fatih Arslan,Ruenn Chai Lai,Ruenn Chai Lai,Mirjam B. Smeets,Lars Akeroyd,Andre Choo,Eissa N. E. Aguor,Leo Timmers,Harold V.M. van Rijen,Pieter A. Doevendans,Gerard Pasterkamp,Sai Kiang Lim,Dominique P.V. de Kleijn +12 more
TL;DR: This study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury, and Hence, mesenchymal stem cell-derived exosome are a potential adjuvant to reperfusion therapy for my cardiac infarction.
Journal ArticleDOI
Mesenchymal Stem Cells Biology, Pathophysiology, Translational Findings, and Therapeutic Implications for Cardiac Disease
TL;DR: The current understanding of MSC biology, mechanism of action in cardiac repair, translational findings, and early clinical trial data of M SC therapy for cardiac disease are reviewed.
References
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