Induction of bone marrow-derived cells myogenic identity by their interactions with the satellite cell niche

Abstract

BackgroundSkeletal muscle regeneration is possible thanks to unipotent stem cells, which are satellite cells connected to the myofibers. Populations of stem cells other than muscle-specific satellite cells are considered as sources of cells able to support skeletal muscle reconstruction. Among these are bone marrow-derived mesenchymal stem cells (BM-MSCs), which are multipotent, self-renewing stem cells present in the bone marrow stroma. Available data documenting the ability of BM-MSCs to undergo myogenic differentiation are not definitive. In the current work, we aimed to check if the satellite cell niche could impact the ability of bone marrow-derived cells to follow a myogenic program.MethodsWe established a new in-vitro method for the coculture of bone marrow-derived cells (BMCs) that express CXCR4 (CXCR4+BMCs; the stromal-derived factor-1 (Sdf-1) receptor) with myofibers. Using various tests, we analyzed the myogenic identity of BMCs and their ability to fuse with myoblasts in vitro and in vivo.ResultsWe showed that Sdf-1 treatment increased the number of CXCR4+BMCs able to bind the myofiber and occupy the satellite cell niche. Moreover, interaction with myofibers induced the expression of myogenic regulatory factors (MRFs) in CXCR4+BMCs. CXCR4+BMCs, pretreated by the coculture with myofibers and Sdf-1, participated in myotube formation in vitro and also myofiber reconstruction in vivo. We also showed that Sdf-1 overexpression in vivo (in injured and regenerating muscles) supported the participation of CXCR4+BMCs in new myofiber formation.ConclusionWe showed that CXCR4+BMC interaction with myofibers (that is, within the satellite cell niche) induced CXCR4+BMC myogenic commitment. CXCR4+BMCs, pretreated using such a method of culture, were able to participate in skeletal muscle regeneration.

Hypoxic Preconditioned Bone Marrow-Derived Mesenchymal Stromal/Stem Cells Enhance Myoblast Fusion and Skeletal Muscle Regeneration

“…As we mentioned above, bone marrow-derived MSCs do not present naïve myogenic potential (45). These cells do not fuse in the absence of myoblasts and rarely fuse with myoblasts in co-cultures (45,(50)(51)(52)(53). However, bone marrow-derived MSCs could follow myogenic differentiation as the result of reprogramming induced by 5-azacytidine treatment, overexpression of Notch intracellular domain (NICD), paired box transcription factor 3 (Pax3), or constitutively active β-catenin, or as a result of 3D co-culture with myofibers (54)(55)(56)(57)(58)(59).…”

The Role of MSCs and Cell Fusion in Tissue Regeneration

“…MSCs do not possess myogenic differentiation capacity, but they are able to fuse to myoblasts to a small extent [54]. Differentiation capacity can be induced by the overexpression of Pax3 or β-catenin and by the satellite cell niche, but not by the niche's factors IGF-1, IL-4, IL-6 or SDF-1 [55][56][57][58]. Additionally, MSCs showed a positive effect on muscle regeneration in Duchenne muscular dystrophy model mice by secreting the chemokine CXCL12 and osteopontin [59].…”

Biological Basis of Treatments of Acute Muscle Injuries: A Short Review

“…They have the capacity to differentiate into multinucleated myotubes and heal muscle injury in a mice model. 37 Mesenchymal stem cells (MSCs) obtained from bone marrow, 38 adipose tissue, placenta, and umbilical cord have been investigated in animal studies. They have multiple theoretical advantages.…”