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...

Full description

Bibliographic Details
Main Authors: Daniel J. Weiss, Karen English, Anna Krasnodembskaya, Johana M. Isaza-Correa, Ian J. Hawthorne, Bernard P. Mahon
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.01228/full
id doaj-a06b1000da9c494785bb96605f147a5c
record_format Article
spelling 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
work_keys_str_mv AT danieljweiss thenecrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT karenenglish thenecrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT annakrasnodembskaya thenecrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT johanamisazacorrea thenecrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT ianjhawthorne thenecrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT bernardpmahon thenecrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT danieljweiss necrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT karenenglish necrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT annakrasnodembskaya necrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT johanamisazacorrea necrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT ianjhawthorne necrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
AT bernardpmahon necrobiologyofmesenchymalstromalcellsaffectstherapeuticefficacy
_version_ 1716807640873435136