Functional Recovery Induced by Satellite Cell Grafts in Irreversibly Injured Muscles

Abstract

Grafting autologous cultured satellite cells in irreversibly injured rat extensor digitorum longus EDL muscle leads to myofiber regeneration at the grafting site. In this study, we investigated whether cell grafts induced functional improvement and correlated mechanophysiological findings with histological observations. In cell grafted muscles, the number of myofibers did not differ significantly between 2 wk and 3 mo, whereas no regenerating myofibers were observed in ungrafted controls. During this period, the total number of myofibers in the cell grafted muscles represented 48.2-51.9% of that in normal muscles. The mean diameter of regenerated myofibers increased with time, reaching a maximum (32 microns) at the second mo and remained smaller than that of normal myofibers (47 microns). Muscle function was measured by mechanophysiological recordings of muscle response to supramaximal electrical stimulation of the nerve in situ. Cell grafted muscles exhibited a progressive improvement of all contractile parameters. After 3 mo, a 4-fold increase in absolute values of twitch and tetanic tension outputs was measured in cell grafted muscles when compared to ungrafted controls. However, these parameters remained much lower than in normal muscles (23.4% and 22.3% of control, respectively). This study showed that myogenic cell grafts replace degenerated myofibers and form functional myofibers. Functional improvement observed, between 2 wk and 3 mo after cell grafting, correlated with the development, differentiation, and maturation of the regenerated myofibers rather than with an increase in the number of regenerated myofibers.

Use of Repeating Dispensers to Increase the Efficiency of the Intramuscular Myogenic Cell Injection Procedure

“…The most important are ery of small volumes of liquid as cell injection devices to accelerate and facilitate the task of injecting mythe therapeutic management of genetic recessive myopathies (5,11,12), traumatized skeletal muscles with myooblasts. fiber loss (1,2), and ischemic cardyopathies (4,7). Col-MATERIALS AND METHODS laterally, genetically modified myoblasts transplanted Animals into skeletal muscles are considered promising vehicles for the systemic or local delivery of hormones or factors Six adult cynomolgus monkeys (Macaca fascicularis) were used as receivers for myoblast allotransplan- (3,8,9,18).…”

Functional improvement of damaged adult mouse muscle by implantation of primary myoblasts.

“…MCs from primary cultures have been shown to survive and differentiate after implantation in the mouse (Watt, Lambert, Morgan, Partridge & Sloper, A. Irintchev, M. Langer, M. Zweyer, R. Theisen and A. Wernig 1982;Morgan, Hoffman & Partridge, 1990; Huard, Labrecque, Dansereau, Robitaille & Tremblay, 1991;Rando & Blau, 1994;Huard et al 1994) but functional effects have not been investigated. Only one study shows improvement of contractile parameters of damaged and X-ray irradiated muscles in the rat (Alameddine, Louboutin, Dehaupas, Sebille & Fardeau, 1994). It should be pointed out that in most previous studies in the mouse, mixtures of different cell types, rather than pure myoblast cultures, have been implanted.…”

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

“…So far, this property was unequivocally confirmed only in transplantation of myoblasts. Myoblast transplantation was the only type of myogenic cell transplantation in mice that was able to completely or almost completely regenerate muscles destroyed by different acute treatments, recovering muscle mass and strength [19][20][21][22]. Nevertheless, these acute experimental conditions are different from a chronic degenerative myopathy.…”

“…In the absence of intrinsic competitors for myofiber regeneration, the participation of grafted cells seems to be favored. The most frequent experimental method to inhibit the proliferation of the satellite cells is to submit the skeletal muscles to high doses of ionizing radiation before transplantation [9,19,20,139,142]. Another possibility (more accessible to laboratories that do not have access to irradiation equipment) is cryodamage.…”