Xenogeneic transplantation of human adipose-derived stem cell sheets accelerate angiogenesis and the healing of skin wounds in a Zucker Diabetic Fatty rat model of obese diabetes

人类脂肪干细胞片异种移植加速肥胖糖尿病 Zucker 糖尿病脂肪大鼠模型的血管生成和皮肤伤口愈合

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作者:Mariko Hamada, Takanori Iwata, Yuka Kato, Kaoru Washio, Shunichi Morikawa, Hiroyuki Sakurai, Masayuki Yamato, Teruo Okano, Yasuko Uchigata

Conclusion

This xenograft model may contribute to the use of human cell tissue-based products (hCTPs) and the identification of factors produced by hCTPs that accelerate wound healing.

Methods

We developed an optimized protocol to engineer hASC sheets using temperature-responsive culture dishes to enhance the function and stability of transplanted cells used for regenerative medicine. Here, we evaluated the efficacy of hASC sheets for enhancing wound healing. For this purpose, we used a xenogeneic model of obese type 2 diabetes, the Zucker Diabetic Fatty rat (ZDF rat), which displays full-thickness skin defects. We isolated hASCs from five donors, created hASC sheets, and transplanted the hASC sheets along with artificial skin into full-thickness, large skin defects (15-mm diameter) of ZDF rats.

Results

The hASC sheets secreted angiogenic growth factors. Transplantation of the hASC sheets combined with artificial skin increased blood vessel density and dermal thickness, thus accelerating wound healing compared with that in the controls. Immunohistochemical analysis revealed significantly more frequent neovascularization in xenografted rats of the transplantation group, and the transplanted hASCs were localized to the periphery of new blood vessels.

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