Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury

Scully, David; Sfyri, Peggy; Verpoorten, Sandrine; Papadopoulos, Petros; Muñoz-Turrillas, María Carmen; Mitchell, Robert; Aburima, Ahmed; Patel, Ketan; Gutiérrez, Laura; Naseem, Khalid M.; Matsakas, Antonios

Abstract

Aim

The use of platelets as biomaterials has gained intense research interest. However, the mechanisms regarding platelet‐mediated skeletal myogenesis remain to be established. The aim of this study was to determine the role of platelet releasate in skeletal myogenesis and muscle stem cell fate in vitro and ex vivo respectively.

Methods

We analysed the effect of platelet releasate on proliferation and differentiation of C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by determining the effect of platelet releasate on murine skeletal muscle stem cells using protein expression profiles for key myogenic regulatory factors.

Results

TRAP6 and collagen used for releasate preparation had a more pronounced effect on myoblast proliferation versus thrombin and sonicated platelets (P less than 0.001). Platelet releasate was detrimental for myoblast fusion and affected differentiation of myoblasts in a temporal manner. Most importantly we show that platelet releasate promotes skeletal myogenesis through the PDGF/VEGF‐Cyclin D1‐MyoD‐Scrib‐Myogenin axis and accelerates skeletal muscle regeneration after acute injury.

Conclusion
This study provides novel mechanistic insights on the role of platelet releasate in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials in regenerative medicine.

Citation

Scully, D., Sfyri, P., Verpoorten, S., Papadopoulos, P., Muñoz-Turrillas, M. C., Mitchell, R., Aburima, A., Patel, K., Gutiérrez, L., Naseem, K. M., & Matsakas, A. (2019). Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury. Acta Physiologica, 225(3), Article e13207. https://doi.org/10.1111/apha.13207

• Journal Article Type: Article
• Acceptance Date: Oct 19, 2018
• Online Publication Date: Nov 14, 2018
• Publication Date: 2019-03
• Deposit Date: Oct 23, 2018
• Publicly Available Date: Nov 15, 2019
• Journal: Acta Physiologica
• Print ISSN: 1748-1708
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 225
• Issue: 3
• Article Number: e13207
• DOI: https://doi.org/10.1111/apha.13207
• Keywords: Growth factors; Platelet releasate; Platelet‐rich plasma; Regeneration; Skeletal muscle; Satellite cells
• Public URL: https://hull-repository.worktribe.com/output/1125975
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.13207
• Contract Date: Oct 24, 2018