Abstract
BackgroundThe skeletal muscle regeneration relays on the satellite cells which are stem cells located between basal lamina and plasmalemma of muscle fiber. In the injured muscles, the satellite cells become activated, start to proliferate, and then differentiate into myoblasts, which fuse to form myotubes and finally myofibers. The satellite cells play the crucial role in the regeneration; however, other cells present in the muscle could also support this process. In the present study, we focused on one population of such cells, i.e., muscle interstitial progenitor cells.MethodsWe used the CD146 marker to identify the population of mouse muscle interstitial cells. We analyzed the expression of selected markers, as well as clonogenic, myogenic, adipogenic, and chondrogenic potential in vitro. Simultaneously, we analyzed satellite cell-derived myoblasts and bone marrow-derived mesenchymal stem/stromal cells that allowed us to pinpoint the differences between these cell populations. Moreover, we isolated CD146+ cells and performed heterotopic transplantations to follow their in vivo differentiation.ResultsMouse muscle CD146+ interstitial progenitor cells expressed nestin and NG2 but not PAX7. These cells presented clonogenic and myogenic potential both in vitro and in vivo. CD146+ cells fused also with myoblasts in co-cultures in vitro. However, they were not able to differentiate to chondro- or adipocytes in vitro. Moreover, CD146+ cells followed myogenic differentiation in vivo after heterotopic transplantation.ConclusionMouse CD146+ cells represent the population of mouse muscle interstitial progenitors that differ from satellite cell-derived myoblasts and have clonogenic and myogenic properties.
Highlights
The skeletal muscle regeneration relays on the satellite cells which are stem cells located between basal lamina and plasmalemma of muscle fiber
It should be noticed that except differences in marker expression, these cells have diverse clonogenic and differentiation potential and, as a result, the role in skeletal muscle homeostasis [12]. Among such cells are fibro-adipogenic progenitors (FAPs), characterized on the basis of platelet-derived growth factor receptor α (PDGFRα), β (PDGFRβ), CD34, stem cell antigen-1 (Sca1) expression, and presenting the ability to differentiate into fibroblasts and adipocytes [12, 13]
We used the CD146 marker to isolate the population of mouse muscle interstitial progenitor cells (MIPCs)
Summary
The skeletal muscle regeneration relays on the satellite cells which are stem cells located between basal lamina and plasmalemma of muscle fiber. Another population of interstitial myogenic progenitors, described in mouse muscles, consists of TWIST2+ cells [17] These cells participate in myofibers formation during skeletal muscle regeneration and effectively fuse with each other in vitro, in the absence of myoblasts [17]. Sacchetti and coworkers described the population of human CD146+ clonogenic myogenic progenitors, localized as adventitial reticular cells in the microvascular compartment in human muscles, i.e., with characteristic similar to pericytes [28] These cells followed the myogenic program in vitro, spontaneously forming myotubes and expressing myogenic factors (PAX7 and MYF5) and myosin heavy chains, and were able to undergo myogenic differentiation after their heterotopic or orthotopic transplantation [28]
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