Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy
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SKELETAL DEGENERATION AND REGENERATION (M PEI, SECTION EDITOR)
Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy Yajun Liu 1 & Qian Chen 1 Accepted: 16 October 2020 # Springer Nature Switzerland AG 2020
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. Keywords Mesenchymal stem cells . Cell senescence . Replication stress . Age-associated diseases . Senolytics . Osteoarthritis
Introduction Mesenchymal stem/stromal cells (MSCs) are tissue-specific progenitor cells with self-renewal abilities and multi-potent differentiation potentials, which make them one of the key players in maintaining tissue and organ homeostasis [1]. MSCs can be found in a variety of tissues, including bone marrow, adipose tissue, cartilage, dental pulp, umbilical cord blood, and placenta [1]. Thus they can differentiate into multiple cell lineages, such as bone, cartilage, adipose, and neuron cells [1]. Due to their easy isolation and expansion, MSCs have shown increasing promise for clinical application [1]. In the last few years, MSCs have emerged as powerful tools in their use as seed cells for therapeutic applications in This article is part of the Topical Collection on Skeletal Degeneration and Regeneration * Qian Chen [email protected] 1
Laboratory of Molecular Biology and Nanomedicine, Department of Orthopaedics, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA
tissue engineering and regenerative medicine [2]. Due to their low immunogenicity, MSCs can be safely transplanted autologously or allogeneically [3]. They have been applied to the treatment of different diseases, such as graft vs. host disease (GVHD), diabetes mellitus (DM), Crohn’s disease (CD), multiple sclerosis (MS), and myocardial infarction (MI) [2]. Despite the huge advances made in the field, a
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