Efficacy of xeno-free induced mesenchymal stem/stromal cells in enhancing autologous fat graft survival

Breast reconstruction using autologous fat grafting offers a less invasive alternative with shorter surgical times compared to traditional flap procedures. Although adipose-derived stem cells (ASCs) have improved fat graft survival rates, the variability in mesenchymal stem cells (MSCs) quality due to donor health and medication intake poses challenges. MSCs derived from induced pluripotent stem cells (iPSC-MSCs) demonstrate enhanced proliferative and immunomodulatory properties that may further enhance outcomes. We harvested human adipose tissue from surgical specimens and isolated ASCs. We used human iPSC-MSCs generated through a neural crest cell lineage under xeno-free conditions (iMSCs), to assess the improvement in survival and integration of autologous human adipose tissue grafts in BALB/c-nu/ + mice. We compared outcomes in groups treated with phosphate-buffered saline (PBS), ASCs, and iMSCs over 28 days, focusing on fat graft retention, fibrosis, and neovascularization, and adipogenic differentiation using vimentin/perilipin immunofluorescence staining. iMSC treatment significantly preserved graft area (82.3 ± 20.5%) compared to PBS controls (50.6 ± 28.7%) and ASC treatments (65.3 ± 24.7%). It also resulted in the lowest fibrosis (7,748.7 ± 6,018.6 µm2) and highest neovascularization (68,681.5 ± 21,363.4 µm2), indicating improved tissue integration and vascularization. The proportion of vimentin-positive/perilipin-positive cells—indicative of adipogenic differentiation—was significantly higher in the iMSC group (7.46%) compared to PBS (4.51%, p = 0.025). iMSCs may enhance fat graft survival through both paracrine signaling and adipogenic differentiation, supporting a dual mechanism of action. These findings highlight their potential as a standardized, high-performance cellular adjunct for improving surgical outcomes in breast reconstruction and potentially other regenerative medicine applications. Further studies incorporating cell tracking techniques are warranted to confirm the direct differentiation potential of iMSCs.