Comparable Effects on Healing between Autologous Diabetic Adipose-Derived Stem Cells and Allogeneic Normal Counterparts

Abstract

Background: Adipose-derived stem cell (ASC) therapy is considered a promising strategy for improving impaired wound healing, especially in diabetics. Although the therapeutic potential of allogeneic ASCs from healthy donors is naturally limited, that of autologous ASCs from diabetic patients is questionable. The aim of this study was to investigate the impact of diabetic ASCs in the treatment of diabetic wounds. Methods: Diabetic ASCs (DMA) and nondiabetic ASCs were isolated from db/db and C57BL/6J mice, and characterized by immunocytochemistry, proliferation, differentiation, and gene expression assays. The effects of both ASCs on healing were investigated using 36 male 10- to 12-week-old db/db mice. Wound size was measured semiweekly until day 28, and histologic and molecular analyses were performed at day 14. Results: Both ASCs had fibroblast-like morphology and were CD44+/CD90+/CD34−/CD45− at passage 4. Compared with nondiabetic ASCs in vitro, DMA proliferative capability was restored by passage 4 (P > 0.05). Although DMA osteogenesis was attenuated (P < 0.01), both ASCs had similar adipogenesis and expressions of PPARγ/LPL/OCN/RUNX2 (P > 0.05). In vivo experiments showed that, compared with phosphate-buffered saline control, both ASCs are comparable in improving wound healing (P < 0.0001), angiogenesis (P < 0.05), epithelial cell proliferation (P < 0.05), and granulation tissue formation (P < 0.0001). Conclusions: In both in vitro and in vivo murine models, DMAs have shown a comparable therapeutic capacity to normal ASCs in promoting diabetic wound healing by improving angiogenesis, reepithelialization, and granulation tissue formation. These results support clinical applications of autologous ASCs in diabetic wound treatments. Clinical Relevance Statement: This work has particular surgical relevance as it highlights a theoretical and clinical pathway to use diabetic patients’ own ASCs to treat their wounds, bypassing any concerns of cross-host sourcing issues in regenerative medicine.