Abstract
Muscle stem cells (MuSC) are considered as a reliable source of therapeutic cells to restore diseased muscles. However in most cases, injected MuSC-derived myoblasts are rapidly destroyed by the host immune response, which impairs the beneficial effect. By contrast, human mesenchymal stromal cells (MSC), have been reported to exhibit potent immune regulatory functions. Thus, we investigated, in vitro, the multipotent differentiation- and immunosuppressive capacities of human myoblasts and compared these features with those of human MSC. Myoblasts shared numerous cell surface markers with MSC, including CD73, CD90, CD105 and CD146. Both cell type were negative for HLA-DR and CD45, CD34 and CD31. CD56, a myogenic marker, was expressed by myoblasts exclusively. Myoblasts displayed multipotent potential capabilities with differentiation in chondrocytes, adipocytes and osteoblasts in vitro. Myoblasts also inhibited allogenic T cell proliferation in vitro in a dose dependent manner, very similarly to MSC. This effect was partly mediated via the activation of indolamine 2,3 dioxygenase enzyme (IDO) after IFNγ exposure. Altogether, these data demonstrate that human myoblasts can differentiate in various mesenchymal linages and exhibit powerful immunosuppressive properties in vitro. Such features may open new therapeutic strategies for MuSC-derived myoblasts.
Highlights
Muscle stem cells (MuSC), known as satellite cells (SC), are heterogenous and quiescent tissue-resident cells [1], essential for skel etal muscle regeneration [2,3]
MuSC represent a powerful source of stem cells for cell-based therapies, as suggested by an initial study showing that the injection of MuSC-derived myoblasts restored dystrophin expression in dystrophic mice [4]
We demonstrated that human myogenic stem cells, generated in vitro, are similar to quiescent MuSC with properties required for their use in cell therapy, i.e they survive, they regenerate damaged myofibers and they can replenish the MuSC pool [20]
Summary
Muscle stem cells (MuSC), known as satellite cells (SC), are heterogenous and quiescent tissue-resident cells [1], essential for skel etal muscle regeneration [2,3]. In a first “in-human” clinical trial, intra-arterial delivery of human mesoangio blasts in dystrophic patients was found to be safe, but of little clinical benefit [18]. These studies have highlighted the importance of injecting quiescent MuSC to patients rather than MuSC-derived myoblasts, that actively divided and partially lost their regenerative potential in vivo [19]. After injection in injured muscles, depending on the environmental cues, MuSC get rapidly activated and generate myoblasts that contribute to the regeneration process. MuSC-derived myoblasts express surface molecules such as major histocompatibility complex (MHC) class II, ICAM-1 and B7–H1/PDL-1 [21] which are expected to either stimulate or inhibit T cell activation, indicating that the fate of the injected cells depends upon complex molecular interactions
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