Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation

Abstract

BackgroundSkeletal muscle has a remarkable regenerative capacity. However, extensive damage that exceeds the self-regenerative ability of the muscle can lead to irreversible fibrosis, scarring, and significant loss of function. Adipose-derived stem cells (ADSC) are a highly abundant source of progenitor cells that have been previously reported to support the regeneration of various muscle tissues, including striated muscles. The aim of this study was to evaluate the effect of ADSC transplantation on functional skeletal muscle regeneration in an acute injury model.MethodsMouse ADSC were isolated from subcutaneous fat tissue and transplanted with a collagen hydrogel into the crushed tibialis anterior muscle of mice. Recovering muscles were analyzed for gene and protein expression by real-time quantitative polymerase chain reaction and immunohistochemistry. The muscle contractility was assessed by myography in an organ bath system.ResultsIntramuscular transplantation of ADSC into crushed tibialis anterior muscle leads to an improved muscle regeneration with ADSC residing in the damaged area. We did not observe ADSC differentiation into new muscle fibers or endothelial cells. However, the ADSC-injected muscles had improved contractility in comparison with the collagen-injected controls 28 days post-transplantation. Additionally, an increase in fiber cross-sectional size and in the number of mature fibers with centralized nuclei was observed.ConclusionsADSC transplantation into acute damaged skeletal muscle significantly improves functional muscle tissue regeneration without direct participation in muscle fiber formation. Cellular therapy with ADSC represents a novel approach to promote skeletal muscle regeneration.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0922-1) contains supplementary material, which is available to authorized users.

Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice

“…Although differentiation towards mature spermatozoa could not be proven, these results confirm its critical regulatory role during spermatogenesis [ 23 ]. A similar observation was reported recently when treating acute muscle injury in mice with autologous transplantation of adipose tissue-derived MSCs [ 34 ]. Muscle regeneration was improved, but the direct differentiation of MSCs was never observed.…”

“…Muscle regeneration was improved, but the direct differentiation of MSCs was never observed. The regenerative potential was attributed to paracrine factors secreted by MSCs [ 34 ].…”

Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage

“…While local injection might come with a higher potential for targeted cell integration, it is difficult to achieve for diseases where different organs or large parts of the body are affected, as it is true for most neuromuscular disorders (Gois et al, 2019). On the other hand, while systemic application might have a drawback in the entrapment of most injected cells in organs such as lungs and liver (Gois et al, 2019) recent studies suggest that a principal function of stem cell therapies relies in their modulatory activities on cellular signaling rather than direct cell engraftment (Gorecka et al, 2018;Boldyreva et al, 2019;Mitchell et al, 2019;Torres-Torrillas et al, 2019). Although in different animal models and clinical applications beneficial effects of stem cell grafts on recovery of muscle tissue were reported (Forcales, 2015;Torres-Torrillas et al, 2019), little emphasis has been put on their impact at the level of the neuromuscular junction (NMJ).…”

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]. Even so, there is a shortage of literature regarding the application of AMSCs in muscular injuries.…”