The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy
Rapid progress is occurring in understanding the mechanisms underlying mesenchymal stromal cell (MSC)-based cell therapies (MSCT). However, the results of clinical trials, while demonstrating safety, have been varied in regard to efficacy. Recent data from different groups have shown profound and si...
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doaj-a06b1000da9c494785bb96605f147a5c2020-11-24T20:48:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01228454188The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic EfficacyDaniel J. Weiss0Karen English1Anna Krasnodembskaya2Johana M. Isaza-Correa3Ian J. Hawthorne4Bernard P. Mahon5Department of Medicine, University of Vermont College of Medicine, Burlington, VT, United StatesCellular Immunology Laboratory, Biology Department, Human Health Research Institute, Maynooth University, Maynooth, IrelandSchool of Medicine, Dentistry and Biomedical Sciences, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast, United KingdomImmunology & Cell Biology Laboratory, Biology Department, Human Health Research Institute, Maynooth University, Maynooth, IrelandCellular Immunology Laboratory, Biology Department, Human Health Research Institute, Maynooth University, Maynooth, IrelandImmunology & Cell Biology Laboratory, Biology Department, Human Health Research Institute, Maynooth University, Maynooth, IrelandRapid progress is occurring in understanding the mechanisms underlying mesenchymal stromal cell (MSC)-based cell therapies (MSCT). However, the results of clinical trials, while demonstrating safety, have been varied in regard to efficacy. Recent data from different groups have shown profound and significant influences of the host inflammatory environment on MSCs delivered systemically or through organ-specific routes, for example intratracheal, with subsequent actions on potential MSC efficacies. Intriguingly in some models, it appears that dead or dying cells or subcellular particles derived from them, may contribute to therapeutic efficacy, at least in some circumstances. Thus, the broad cellular changes that accompany MSC death, autophagy, pre-apoptotic function, or indeed the host response to these processes may be essential to therapeutic efficacy. In this review, we summarize the existing literature concerning the necrobiology of MSCs and the available evidence that MSCs undergo autophagy, apoptosis, transfer mitochondria, or release subcellular particles with effector function in pathologic or inflammatory in vivo environments. Advances in understanding the role of immune effector cells in cell therapy, especially macrophages, suggest that the reprogramming of immunity associated with MSCT has a weighty influence on therapeutic efficacy. If correct, these data suggest novel approaches to enhancing the beneficial actions of MSCs that will vary with the inflammatory nature of different disease targets and may influence the choice between autologous or allogeneic or even xenogeneic cells as therapeutics.https://www.frontiersin.org/article/10.3389/fimmu.2019.01228/fullmesenchymal stromal cellcell therapyapoptosisautophagymitochondriaextracellular vesicles |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel J. Weiss Karen English Anna Krasnodembskaya Johana M. Isaza-Correa Ian J. Hawthorne Bernard P. Mahon |
spellingShingle |
Daniel J. Weiss Karen English Anna Krasnodembskaya Johana M. Isaza-Correa Ian J. Hawthorne Bernard P. Mahon The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy Frontiers in Immunology mesenchymal stromal cell cell therapy apoptosis autophagy mitochondria extracellular vesicles |
author_facet |
Daniel J. Weiss Karen English Anna Krasnodembskaya Johana M. Isaza-Correa Ian J. Hawthorne Bernard P. Mahon |
author_sort |
Daniel J. Weiss |
title |
The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy |
title_short |
The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy |
title_full |
The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy |
title_fullStr |
The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy |
title_full_unstemmed |
The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy |
title_sort |
necrobiology of mesenchymal stromal cells affects therapeutic efficacy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-06-01 |
description |
Rapid progress is occurring in understanding the mechanisms underlying mesenchymal stromal cell (MSC)-based cell therapies (MSCT). However, the results of clinical trials, while demonstrating safety, have been varied in regard to efficacy. Recent data from different groups have shown profound and significant influences of the host inflammatory environment on MSCs delivered systemically or through organ-specific routes, for example intratracheal, with subsequent actions on potential MSC efficacies. Intriguingly in some models, it appears that dead or dying cells or subcellular particles derived from them, may contribute to therapeutic efficacy, at least in some circumstances. Thus, the broad cellular changes that accompany MSC death, autophagy, pre-apoptotic function, or indeed the host response to these processes may be essential to therapeutic efficacy. In this review, we summarize the existing literature concerning the necrobiology of MSCs and the available evidence that MSCs undergo autophagy, apoptosis, transfer mitochondria, or release subcellular particles with effector function in pathologic or inflammatory in vivo environments. Advances in understanding the role of immune effector cells in cell therapy, especially macrophages, suggest that the reprogramming of immunity associated with MSCT has a weighty influence on therapeutic efficacy. If correct, these data suggest novel approaches to enhancing the beneficial actions of MSCs that will vary with the inflammatory nature of different disease targets and may influence the choice between autologous or allogeneic or even xenogeneic cells as therapeutics. |
topic |
mesenchymal stromal cell cell therapy apoptosis autophagy mitochondria extracellular vesicles |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.01228/full |
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