Application of fetal neural stem cells transplantation in delaying denervated muscle atrophy in rats with peripheral nerve injury.
Injury to peripheral nerves always results in progressive skeletal muscle atrophy and poor functional recovery. Previous studies have demonstrated that transplanting neural stem cells (NSCs) into peripheral nerve can differentiate into neurons and delay muscle atrophy. However, the mechanism was not very clear. In this study, we transplanted the fetal NSCs to the injured nerve and examined new formed neuromuscular junctions (NMJs) in the denervated muscle and arrest of muscle atrophy. In our study, two pregnant Fischer rats were used to harvest fetal NSCs, 70 rats were randomly divided into NSC-transplanted and control groups, five rats without surgery were used as the normal control. A volume of 5 microl culture media with or without fetal NSCs (5 x 10(6)) were transplanted into distal tibial nerve stump after the nerve was transected in two groups, respectively. Three, five, and seven months after denervation, the dry weight of gastrocnemius muscle was found significant heavier, and the fiber area was more retained in NSC-transplanted group comparing to the control group (P < 0.05). Neurons were found in the distal tibial nerves even 7 months after fetal NSCs transplantation. Newly formed NMJs were detected by immunohistochemistry. In addition, the results of electrophysiological analysis and retrograde tracing manifested that the neural pathway between muscle and differentiated neurons was integrity. In conclusions, our study demonstrated that fetal NSCs transplanted into peripheral nerves could differentiate into neurons and form functional NMJs with denervated muscle, which may be beneficial for the treatment of muscle atrophy after peripheral nerve injury.
Gu
Shihui
S
Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Shen
Yundong
Y
Xu
Wendong
W
Xu
Lei
L
Li
Xiaokang
X
Zhou
Guoming
G
Gu
Yudong
Y
Xu
Jianguang
J
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D008297:Male; D009121:Muscle Denervation; D009133:Muscular Atrophy / Q000517:prevention & control*; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000637:transplantation; D059348:Peripheral Nerve Injuries; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D018570:Risk Assessment; D033581:Stem Cell Transplantation / Q000379:methods*; D013979:Tibial Nerve / Q000293:injuries* / Q000601:surgery; D014951:Wounds, Stab / Q000628:therapy*