Biosponge-Encased Placental Stem Cells for Volumetric Muscle Loss Repair

Objective: Volumetric muscle loss (VML) leads to permanent muscle mass and functional impairments. While mesenchymal stromal cells (MSCs) and their secreted factors can aid muscle regeneration, MSCs exhibit limited persistence in injured tissue post-transplantation. Human placental-derived stem cells (hPDSCs), sharing surface markers with MSCs, demonstrate superior regenerative potential due to their fetal origin. Previously, a biosponge (BS) scaffold was shown to augment muscle regeneration post-VML. This study aims to coapply BS therapy and hPDSCs to further enhance muscle recovery following VML. Approach: A VML defect was created by removing ∼20% of the tibialis anterior muscle mass in male Lewis rats. Injured muscles were either left untreated or treated with BS or BS-encapsulated hPDSCs cultured under normoxic or hypoxic conditions. On day 28 postinjury, peak isometric torque was measured, and the muscle was harvested for analysis. Results: BS encapsulated hPDSCs subjected to hypoxic preconditioning persisted in larger quantities and enhanced muscle mass at day 28 postinjury. BS encapsulated hPDSCs cultured under normoxic or hypoxic conditions increased small myofibers (<500 µm²) percentage, MyoD protein expression, and both pro- and anti-inflammatory macrophage marker expression. BS encapsulated hPDSCs also reduced fibrosis and BS remodeling rate. Innovation: This study is the first to examine the therapeutic effects of hPDSCs in a rat VML model. A BS carrier and hypoxic preconditioning were investigated to mitigate low cell survival postimplantation. Conclusion: hPDSCs augment the regenerative effect of BS. Combining hPDSCs and BS emerges as a promising strategy worthy of further investigation.