Introduction: Skeletal muscle recovery after prolonged bedrest or disuse is impaired in older adults, negatively impacting quality of life. Prior studies have shown that during muscle recovery, the basement membrane is disrupted, including disorganization of extracellular matrix (ECM) proteins, which may contribute to loss of mechanosensing and fiber regrowth during reload. In the muscle niche, fibro-adipogenic progenitors (FAPs) are primarily responsible for the synthesis of ECM proteins and hence play an important role in muscle structure and function. Recent results from our group suggest that FAP quantity and function is decreased during disuse recovery. Thus, the goal of the study is to determine the extent to which replacement of FAPs immediately prior to remobilization can promote recovery of muscle mass. Methods: FAPs were isolated from young adult (4-month) male (C57BL6/J) mice using CD45-CD31- PDGFRα+ markers and cultured for a week. Young and old (23-month) male (C57BL6/J) mice were subjected to unilateral limb immobilization for 14 days. On Day 14, the immobilized leg was untethered, and 30000 to 50000 cells were injected on the immobilized leg and mice were allowed to roam freely. Tibialis anterior (TA) muscle was excised after predetermined time points and frozen for subsequent analysis. PBS-injected mice served as a control. Cross sectional area (CSA) and fiber type data were collected using MyoVision software. Collagen accumulation was accessed after 7 days of remobilization via immunohistochemistry. Results: FAP transplantation had no effect on muscle weight in young animals but significantly increased the muscle weight of the immobilized limb in aged animals compared to PBS controls. Preliminary CSA data revealed that FAP therapy did not exert a significant increase in the global myofiber CSA, however, a shift towards an oxidative fiber type (Type IIa) was observed in the young animals. While collagen content was not altered in the PBS-treated young animals, aged animals demonstrated elevated collagen levels which was reduced by FAP therapy. Conclusion: These results suggest that FAP therapy may provide beneficial effects for muscle recovery in older adults. Further experimentation will reveal the mechanistic insight behind the significance of FAPs in muscle recovery. Funding: This study was supported by NIAMS of NIH (R01 AR072735). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Vijayan et al. (Fri,) studied this question.