The Myogenic Potential of Mesenchymal Stromal Cells and Their Effect on Skeletal Muscle Regeneration
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BIOLOGY
The Myogenic Potential of Mesenchymal Stromal Cells and Their Effect on Skeletal Muscle Regeneration O. N. Shevelevaa, O. V. Payushinab, *, N. N. Butorinaa, and E. I. Domaratskayaa a
b
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, 119991 Russia *e-mail: [email protected] Received September 20, 2018; revised April 26, 2019; accepted January 31, 2020
Abstract—The participation of mesenchymal stromal cells (MSCs) in the regeneration of muscle tissue was analyzed. It is shown that rat bone marrow MSCs do not show potency for myogenic differentiation in vitro under the influence of appropriate inducers and rarely fuse with myoblasts when co-cultured. However, the factors they release stimulate differentiation of myogenic cells. It is noted that in vivo, when combined with minced muscle tissue, MSCs enhance myogenesis and angiogenesis, and when injected into injured muscle, they improve the course of the recovery process, as well as the medium conditioned by them. The paracrine mechanism of the influence of MSCs on skeletal muscle regeneration has been established. DOI: 10.1134/S106235902005009X
INTRODUCTION Mesenchymal stromal cells (MSCs) as universal regulators of tissue homeostasis are a promising material for regenerative medicine, in particular for the restoration of skeletal muscles after injury. Although skeletal muscle recovery is mainly provided by satellite cells (a resting tissue-specific population of cells), MSCs, both resident and those leaving the bone marrow and entering into the bloodstream, followed by migration to the damaged tissue under the influence of chemoattractants, also participate in the regeneration (Ramírez et al., 2006; Granero-Moltó et al., 2009; Liu et al., 2009; Chen et al., 2010; Fong et al., 2011). Experimental data obtained in recent years indicate that stimulation of muscle regeneration can be achieved by introducing MSCs into the area of injury (Natsu et al., 2004; Winkler et al., 2012; Andrade et al., 2015). Three possible mechanisms of MSC participation in skeletal muscle regeneration are currently under consideration: differentiation in the myogenic direction, fusion with myoblasts, and a paracrine effect on myogenesis. When cultured in the presence of certain inducers, in particular 5-azacytidine (Krupnick et al., 2004), steroid hormones (Gang et al., 2004), and galectin-1 (Chan et al., 2006), MSCs can acquire signs of differentiation into skeletal muscle, expressing the specific markers MyoD (Abcam, United Kingdom) and myogenin and merging into multinucleated
myotubes containing desmin and myosin. However, the capability of MSCs for myogenic differentiation in response to various inducers is not confirmed by all authors and, apparently, is not the same for cells from different organs and at various stages of ontogenesis (Liu et al., 2003; Gang et al., 2004; Balana et al., 2006; Chan et al., 200
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