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Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy

  • Skeletal Degeneration and Regeneration (M Pei, Section Editor)
  • Published:
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Abstract

Purpose of Review

Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic application in tissue engineering and regenerative medicine. Despite their promise, recent findings suggest that MSC replication during repair process may lead to replicative senescence and stem cell exhaustion. Here, we review the basic mechanisms of MSC senescence, how it leads to degenerative diseases, and potential treatments for such diseases.

Recent Findings

Emerging evidence has shown a link between senescent MSCs and degenerative diseases, especially age-related diseases such as osteoarthritis and idiopathic pulmonary fibrosis. During these disease processes, MSCs undergo cell senescence and mediate Senescence Associated Secretory Phenotypes (SASP) to affect the surrounding microenvironment. Thus, senescent MSCs can accelerate tissue aging by increasing the number of senescent cells and spreading inflammation to neighboring cells.

Summary

Senescent MSCs not only hamper tissue repair through cell senescence associated stem cell exhaustion but also mediate tissue degeneration by initiating and spreading senescence-associated inflammation. It suggests new strategies of MSC-based cell therapy to remove, rejuvenate, or replace (3Rs) the senescent MSCs.

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Acknowledgments

This work was supported in part by NIH R61 AR076807 and P30 GM122732 (to Q.C.).

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  1. Laboratory of Molecular Biology and Nanomedicine, Department of Orthopaedics, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, 02903, USA

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Yajun Liu declares no potential conflict of interest. Qian Chen holds patents relevant to human cartilage derived mesenchymal stem cells and is a co-founder of NanoDe Therapeutics Inc.

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Liu, Y., Chen, Q. Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy. Curr Mol Bio Rep 6, 173–182 (2020). https://doi.org/10.1007/s40610-020-00141-0

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