The adipose tissue stromal vascular fraction secretome enhances the proliferation but inhibits the differentiation of myoblasts

Abstract

BackgroundAdipose tissue is an excellent source for isolation of stem cells for treating various clinical conditions including injuries to the neuromuscular system. Many previous studies have focused on differentiating these adipose stem cells (ASCs) towards a Schwann cell-like phenotype (dASCs), which can enhance axon regeneration and reduce muscle atrophy. However, the stromal vascular fraction (SVF), from which the ASCs are derived, also exerts broad regenerative potential and might provide a faster route to clinical translation of the cell therapies for treatment of neuromuscular disorders.MethodsThe aim of this study was to establish the effects of SVF cells on the proliferation and differentiation of myoblasts using indirect co-culture experiments. A Growth Factor PCR Array was used to compare the secretomes of SVF and dASCs, and the downstream signaling pathways were investigated.ResultsSVF cells, unlike culture-expanded dASCs, expressed and secreted hepatocyte growth factor (HGF) at concentrations sufficient to enhance the proliferation of myoblasts. Pharmacological inhibitor studies revealed that the signal is mediated via ERK1/2 phosphorylation and that the effect is significantly reduced by the addition of 100 pM Norleual, a specific HGF inhibitor. When myoblasts were differentiated into multinucleated myotubes, the SVF cells reduced the expression levels of fast-type myosin heavy chain (MyHC2) suggesting an inhibition of the differentiation process.ConclusionsIn summary, this study shows the importance of HGF as a mediator of the SVF effects on myoblasts and provides further evidence for the importance of the secretome in cell therapy and regenerative medicine applications.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1096-6) contains supplementary material, which is available to authorized users.

Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process

“…Our results show that wound healing in SVF-treated mice was significantly more rapid than in control mice, but with no significant difference from the hADSC-treated group. Similar to the literature [28], our results show that SVF contains a percentage of hADSCs. Considering that SVF and hADSC groups use the same number of cells, therefore, it can be inferred that hADSCs in SVF have better activity than expanded hADSCs.…”

Anti-apoptotic effect of adipose tissue-derived stromal vascular fraction in denervated rat muscle

“…In this current study, we hypothesized that injections of freshly isolated adipose-tissue stromal vascular fraction (SVF) would maintain the integrity of the muscle fibers during the period of nerve regeneration. More specifically, we hypothesized that the SVF cell secretome has anti-apoptotic properties, and that combined with its ability to enhance proliferation in vitro [ 9 ], could be one-way muscle atrophy is attenuated in vivo.…”

Adipose-Derived Mesenchymal Stem Cells: A Promising Tool in the Treatment of Musculoskeletal Diseases

“…More recent studies, suggested that AMSCs promote the proliferation of myoblasts, which could explain the regenerative capacity shown in vivo [30,63,64,65,66]. Based in these results, during the last years, some animal models have shown the influence of AMSCs in the treatment of some miopathies [67,68,69,70] and muscular dystrophy [63,65,66].…”

“…After an enzymatic digestion, adipose tissue yields a heterogeneous population of many cell types, which upon isolation are termed the stromal vascular fraction (SVF) [21]. The SVF contain a mixture of regenerative cell types and various immune cells, including preadypocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, resident monocyte, and lymphocytes, but mature adipocytes are absent [28,29,30]. The SVF includes AMSCs, which account for 30% of the total SVF cells [21].…”

“…The SVF includes AMSCs, which account for 30% of the total SVF cells [21]. Some studies have shown improved results with the application of SVF compared to AMSCs, promoting cartilage and subchondral bone regeneration [31], forming new cartilage matrix [32], and enhancing the proliferation of myoblasts [30]. In contrast, SVF inhibits the differentiation of myoblasts [30].…”