Short‐ or long‐term effects of adult myoblast transfer on properties of reinnervated skeletal muscles

Abstract

Skeletal muscle demonstrates a force deficit after repair of injured peripheral nerves. Data from the literature indicate that myoblast transfer enhances recovery of muscle function. Thus, we tested the hypothesis that transfer of adult myoblasts improves the properties of reinnervated rabbit tibialis anterior (TA) muscles in both the short term (4 months) and long term (14 months). Two months after transection and immediate suture of the common peroneal nerve, TA muscles were made to degenerate by cardiotoxin injection and then transplanted with adult myoblasts cultured for 13 days. Under these conditions, muscles studied at 4 months were heavier, contained larger fibers, and developed a significantly higher maximal force than muscles that had only been denervated-reinnervated. In the long term, although muscles made to degenerate were heavier and developed a significantly higher maximal force than denervated-reinnervated muscles, myoblast transfer failed to improve these parameters. However, the overall characteristics of long-term operated muscles tended clearly to approach those of the controls. Taken together, these results may have significant implications in certain orthopedic contexts, particularly after immediate or delayed muscle reinnervation.

Treatment of Tourniquet-Induced Ischemia Reperfusion Injury with Muscle Progenitor Cells

“…Our data suggested that the transplanted MPCs formed myotubes improved muscle function, but did not improve muscle mass. Whether the loss of muscle mass can be reduced when a larger number of cultured MPCs [22] or whether freshly isolated cells are injected [59] remains to be determined.…”

“…The presence of denervated muscle fibers can also increase the proportion of non-contractile elements and decreased specific force [22]. However, it is unlikely that nerve injury contributes to the loss of specific force, as results from our previous study and others showed that nerve injury under similar ischemic condition is only acute and force generated through direct muscle stimulation is similar to that generated through nerve stimulation at 2 wk after TK application, suggesting a lack of nerve injury at this time point [57].…”

“…Another potential source of progenitor cells is skeletal muscle. Transplantation of muscle progenitor cells (MPCs) has been shown to improve muscle function in animal models of muscular diseases, denervation, toxins, cryo-injuries, and volumetric muscle loss [21][22][23][24], and have been used to treat Duchenne dystrophy and cardiovascular diseases in clinical trials [25,26]. Advantages of MPCs as an autologous cell source for transplantation include their abundance in skeletal muscles, high proliferative potential under culture conditions, commitment to myogenic lineage, and high resistance to ischemia [27].…”

Transplantation of Myogenic Cells in Duchenne Muscular Dystrophy Patients

“…This simplicity, to be obtained and expanded in vitro, facilitated the use of myoblasts for cell transplantation. Myoblast transplantation was studied by several different teams in a wide range of animal models such as mice [9], rats [10,11], dogs [12,13], monkeys [14], rabbits [15,16], and pigs [17]. The selective removal of satellite cells in mice makes myofiber regeneration impossible [18][19][20], demonstrating the pivotal and seemingly exclusive role of satellite cells and their progeny, myoblasts, in myofiber regeneration.…”

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

“…So far, myoblasts were the only myogenic cells that were proved unequivocally to engraft in humans and produce myofibers expressing donor-derived dystrophin in DMD patients [10][11][12][13] (Figures 2 and 3). Unlike the other cells that will be described below, myoblasts have been studied by several different teams in a wide range of animal models such as mice [61], rats [62,63], dogs [64,65], monkeys [66], rabbits [67,68], and pigs [69].…”