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    The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy


    Weiss, Daniel J. and English, Karen and Krasnodembskaya, Anna and Isaza-Correa, Johana M. and Hawthorne, Ian J. and Mahon, Bernard P. (2019) The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy. Frontiers in Immunology, 10 (1228). ISSN 1664-3224

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    Abstract

    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.

    Item Type: Article
    Additional Information: © 2019 Weiss, English, Krasnodembskaya, Isaza-Correa, Hawthorne and Mahon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms Cite as: Weiss DJ, English K, Krasnodembskaya A, Isaza-Correa JM, Hawthorne IJ and Mahon BP (2019) The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy. Front. Immunol. 10:1228. doi: 10.3389/fimmu.2019.01228 Funding: DW is funded by the National Institutes of Health (HL127144- 01, EB024329), the Cystic Fibrosis Foundation, and the Medical Technology Consortium. KE is supported by Science Foundation Ireland (SFI) under Grant Number 13/SIRG/2172 through a Starting Investigator Research Grant award and the Irish Research Council Laureate award IRCLA/2017/288. AK is supported by UK Medical Research Council Research Awards (MRC MR/R025096/1 and MR/S009426/1).
    Keywords: mesenchymal stromal cell; cell therapy; apoptosis; autophagy; mitochondria; extracellular vesicles; efficacy;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 13559
    Identification Number: https://doi.org/10.3389/fimmu.2019.01228
    Depositing User: Bernard Mahon
    Date Deposited: 12 Nov 2020 16:34
    Journal or Publication Title: Frontiers in Immunology
    Publisher: Frontiers Media
    Refereed: Yes
    Funders: National Institutes of Health, Cystic Fibrosis Foundation, Medical Technology Consortium, Science Foundation Ireland (SFI), Irish Research Council, UK Medical Research Council Research
    URI:

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