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Review
. 2020 Jul;77(14):2771-2794.
doi: 10.1007/s00018-020-03454-6. Epub 2020 Jan 21.

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Xing-Liang Fan  1 , Yuelin Zhang  2 , Xin Li  2 , Qing-Ling Fu  3   4
Affiliations
Review

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Xing-Liang Fan et al. Cell Mol Life Sci. 2020 Jul.

Abstract

Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies.

Keywords: Cell–cell contact; Extracellular vesicles; Immunomodulation; Integration of MSCs; Mitochondrial transfer; Regenerative potential; Soluble factors.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
MSCs can be isolated from a variety of foetal, neonatal, and adult tissues, and can differentiate into different cell types. CD cluster of differentiation, ESCs embryonic stem cells, iPSCs induced pluripotent stem cells, MSCs mesenchymal stem cells
Fig. 2
Fig. 2
Mechanisms underlying MSC-based therapy. MSCs rescue and/or repair injured cells via differentiation into replacement cell types and by modulating immune responses. The immunomodulatory modes of MSCs include paracrine activity, cell–cell contact and interaction, mitochondrial transfer, and release of extracellular vesicles. The mechanisms involved in repair are not equivalent and MSCs can adapt their therapeutic effects according to diverse local microenvironments. MSCs mesenchymal stem cells
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