Human Muscle-Derived Cells Injected into Acute and Chronic Muscle Injuries Engraft and Support Regenerative Markers

Abstract

Urinary incontinence (UI), the involuntary leakage of urine, is a common condition that imposes significant physical, emotional, and financial burdens. Injury to the external urethral sphincter (EUS) contributes to myogenic UI by damaging the skeletal muscle responsible for urinary control. This study evaluated the engraftment and therapeutic potential of human muscle-derived cells (hMDCs) using acute and chronic skeletal muscle injury models. Immunocompromised female rats received cardiotoxin (CTX) or volumetric muscle loss (VML) injuries to the tibialis anterior muscle. Animals were treated with 100,000 or 500,000 passage 3 or passage 6 hMDCs injected one day after CTX injury or six weeks after VML injury. VivoTrack imaging and human leukocyte antigen staining confirmed successful engraftment of hMDCs at the injection site. A total of 500,000 passage 3 hMDCs reduced muscle force, whereas later-passage 6 cells had no effect on force production. All treatment groups exhibited small, newly regenerated muscle fibers. In chronic VML injuries, hMDC engraftment using 500,000 passage 6 cells enhanced regenerative characteristics despite limited fusion with host muscle fibers. These findings suggest that hMDCs improved regenerative characteristics in a fibrotic VML model but did not restore contractile force. This work supports the therapeutic potential of hMDCs and provides a foundation for future clinical strategies to treat urinary incontinence.