Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle

Mark A Feger; Jonathan Isaacs; Satya Mallu; Dorne Yager; Mary Shall; Gaurangkumar Patel; Omar Protzuk; Akhil S Bokkisam

doi:10.1055/s-0042-1748535

Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle

J Brachial Plex Peripher Nerve Inj. 2022 Jun 21;17(1):e12-e21. doi: 10.1055/s-0042-1748535. eCollection 2022 Jan.

Authors

Mark A Feger¹, Jonathan Isaacs², Satya Mallu², Dorne Yager³, Mary Shall⁴, Gaurangkumar Patel², Omar Protzuk², Akhil S Bokkisam²

Affiliations

¹ Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, United States.
² Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States.
³ Divison of Plastic Surgery, Department of General Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States.
⁴ Department of Physical Therapy, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States.

Abstract

Background 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. Objective The aim of this study is to assess the effect of direct delivery of recombinant FST protein on muscle recovery following muscle reinnervation. Materials and Methods 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. Results Follistatin treatment resulted in smaller muscles after 3 months denervation ( p = 0.019) and reduced force after 3 months sham denervation ( p < 0.001). Conversely, after 6 months of denervation, FST treatment trended toward increased force output ( p = 0.066). Follistatin increased satellite cell counts after denervation ( p < 0.001) but reduced satellite cell counts after sham denervation ( p = 0.037). Conclusion 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.

Keywords: anabolic; denervation atrophy; follistatin; hypertrophy; muscle force; nerve regeneration; nerve repair; peripheral nerve; progenitor cells; rodent.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).

Grants and funding

Funding The study was funded through the Department of Defense, U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Peer Reviewed Orthopaedic Research Program (Award Number: W81XWH-15-1-0229).. Microscopy was performed at the VCU Microscopy Facility, supported, in part, by funding from NIH-NCI Cancer Center Support Grant P30 CA016059.