Mesenchymal Stem Cell Therapy Fails to Improve Fat Graft Retention: Cryopreserved and Cultured Syngeneic and Allogeneic Mesenchymal Stem Cells in a Rat Model.

Abstract

Fat grafting is a gentle technique used to correct soft-tissue defects, but it is challenged by low graft survival rates. To enhance retention, mesenchymal stromal cells (MSCs) have been explored. Autologous MSC therapy has shown promise, but comes with logistical and cost challenges. Allogeneic MSC therapy offers a more feasible solution, with preclinical studies suggesting improved fat graft retention from allogenic MSC therapy. This study aimed to expand the preclinical research by investigating the use of cryopreserved allogeneic MSCs. Using an immunocompetent rat model for autologous fat grafting, the effect of allogeneic MSCs on 3-month fat graft retention was investigated. In a series of experiments, the effect of dosing (0.2 × 10 6 to 25 × 10 6 MSCs/mL), allogenicity (allogeneic and syngeneic), and cryopreservation was assessed. The authors' findings did not indicate any beneficial effect from cryopreserved allogeneic MSC therapy for fat grafting across the tested concentrations. In fact, increasing the dosage resulted in lower fat graft retention, reduced expression of adipose markers, and increased fibrosis. Administration of cryopreserved syngeneic MSCs had no beneficial effect on long-term fat graft retention either. Substituting cryopreserved MSCs with freshly harvested MSCs also did not enhance fat graft retention. Unlike previous preclinical studies, the authors' experiments did not reveal a beneficial effect of supplementing fat grafts with MSCs. Given the limited success in translating MSC-assisted fat grafting to clinical settings, this study underscores the importance of further investigations to evaluate the efficacy of MSC therapy in enhancing fat graft retention. The authors found no benefit of cryopreserved or freshly cultured allogeneic or syngeneic MSC therapy in improving fat graft retention, challenging the clinical relevance of MSC supplementation for fat grafting and suggesting that further research is needed before clinical application.