Feger Mark A, Isaacs Jonathan, Mallu Satya, Yager Dorne, Shall Mary, Patel Gaurangkumar, Protzuk Omar, Bokkisam Akhil S
Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, United States.
Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States.
J Brachial Plex Peripher Nerve Inj. 2022 Jun 21;17(1):e12-e21. doi: 10.1055/s-0042-1748535. eCollection 2022 Jan.
Muscle recovery following peripheral nerve repair is sup-optimal. Follistatin (FST), a potent muscle stimulant, enhances muscle size and satellite cell counts following reinnervation when administered as recombinant FST DNA via viral vectors. Local administration of recombinant FST protein, if effective, would be more clinically translatable but has yet to be investigated following muscle reinnervation. The aim of this study is to assess the effect of direct delivery of recombinant FST protein on muscle recovery following muscle reinnervation. In total, 72 Sprague-Dawley rats underwent temporary (3 or 6 months) denervation or sham denervation. After reinnervation, rats received FST protein (isoform FS-288) or sham treatment via a subcutaneous osmotic pump delivery system. Outcome measures included muscle force, muscle histomorphology, and FST protein quantification. Follistatin treatment resulted in smaller muscles after 3 months denervation ( = 0.019) and reduced force after 3 months sham denervation ( < 0.001). Conversely, after 6 months of denervation, FST treatment trended toward increased force output ( = 0.066). Follistatin increased satellite cell counts after denervation ( < 0.001) but reduced satellite cell counts after sham denervation ( = 0.037). Follistatin had mixed effects on muscle weight and force. Direct FST protein delivery enhanced satellite cell counts following reinnervation. The positive effect on the satellite cell population is intriguing and warrants further investigation.
周围神经修复后的肌肉恢复情况并不理想。卵泡抑素（FST）是一种强效的肌肉刺激剂，通过病毒载体给予重组FST DNA时，可在神经再支配后增加肌肉大小和卫星细胞数量。重组FST蛋白的局部给药若有效，在临床上更具可转化性，但在肌肉神经再支配后尚未进行研究。 本研究的目的是评估直接递送重组FST蛋白对肌肉神经再支配后肌肉恢复的影响。 总共72只Sprague-Dawley大鼠接受了临时（3或6个月）去神经支配或假去神经支配。神经再支配后，大鼠通过皮下渗透泵给药系统接受FST蛋白（异构体FS-288）或假治疗。结果指标包括肌肉力量、肌肉组织形态学和FST蛋白定量。 卵泡抑素治疗导致去神经支配3个月后肌肉较小（ = 0.019），假去神经支配3个月后力量降低（ < 0.001）。相反，去神经支配6个月后，FST治疗有增加力量输出的趋势（ = 0.066）。卵泡抑素在去神经支配后增加了卫星细胞数量（ < 0.001），但在假去神经支配后减少了卫星细胞数量（ = 0.037）。 卵泡抑素对肌肉重量和力量有混合作用。直接递送FST蛋白可在神经再支配后增加卫星细胞数量。对卫星细胞群体的积极作用很有趣，值得进一步研究。
