Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats

This study evaluated the effect of muscle satellite cells (MSCs) overexpressingmyogenin (MyoG) on denervated muscle atrophy. Rat MSCs were isolated and transfectedwith the MyoG-EGFP plasmid vector GV143. MyoG-transfected MSCs (MTMs) weretransplanted into rat gastrocnemius muscles at 1 week after surgical denervation.Controls included injections of untransfected MSCs or the vehicle only. Muscles wereharvested and analyzed at 2, 4, and 24 weeks post-transplantation. Immunofluorescenceconfirmed MyoG overexpression in MTMs. The muscle wet weight ratio was significantlyreduced at 2 weeks after MTM injection (67.17±6.79) compared with muscles injectedwith MSCs (58.83±5.31) or the vehicle (53.00±7.67; t=2.37, P=0.04 and t=3.39,P=0.007, respectively). The muscle fiber cross-sectional area was also larger at 2weeks after MTM injection (2.63×10³±0.39×10³) compared with MSCinjection (1.99×10³±0.58×10³) or the vehicle only(1.57×10³±0.47×10³; t=2.24, P=0.049 and t=4.22, P=0.002,respectively). At 4 and 24 weeks post-injection, the muscle mass and fibercross-sectional area were similar across all three experimental groups.Immunohistochemistry showed that the MTM group had larger MyoG-positive fibers. TheMTM group (3.18±1.13) also had higher expression of MyoG mRNA than other groups(1.41±0.65 and 1.03±0.19) at 2 weeks after injection (t=2.72, P=0.04). TransplantedMTMs delayed short-term atrophy of denervated muscles. This approach can be optimizedas a novel stand-alone therapy or as a bridge to surgical re-innervation of damagedmuscles.