Diabetic Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan
Diabetes. 2015 Aug;64(8):2723-34. doi: 10.2337/db14-1133. Epub 2015 Mar 20.
One of the most common complications of diabetes is diabetic foot ulcer. Diabetic ulcers do not heal easily due to diabetic neuropathy and reduced blood flow, and nonhealing ulcers may progress to gangrene, which necessitates amputation of the patient's foot. This study attempted to develop a new cell-based therapy for nonhealing diabetic ulcers using a full-thickness skin defect in a rat model of type 2 diabetes and obesity. Allogeneic adipose-derived stem cells (ASCs) were harvested from the inguinal fat of normal rats, and ASC sheets were created using cell sheet technology and transplanted into full-thickness skin defects in Zucker diabetic fatty rats. The results indicate that the transplantation of ASC sheets combined with artificial skin accelerated wound healing and vascularization, with significant differences observed 2 weeks after treatment. The ASC sheets secreted large amounts of several angiogenic growth factors in vitro, and transplanted ASCs were observed in perivascular regions and incorporated into the newly constructed vessel structures in vivo. These results suggest that ASC sheets accelerate wound healing both directly and indirectly in this diabetic wound-healing model. In conclusion, allogeneic ASC sheets exhibit potential as a new therapeutic strategy for the treatment of diabetic ulcers.
糖尿病最常见的并发症之一是糖尿病足溃疡。由于糖尿病神经病变和血流减少，糖尿病溃疡不易愈合，而不愈合的溃疡可能进展为坏疽，这需要截肢患者的脚。本研究试图使用 2 型糖尿病和肥胖大鼠的全层皮肤缺损模型为非愈合性糖尿病溃疡开发一种新的基于细胞的治疗方法。从正常大鼠的腹股沟脂肪中收获同种异体脂肪来源的干细胞（ASCs），并使用细胞片技术创建 ASC 片，并将其移植到 Zucker 糖尿病肥胖大鼠的全层皮肤缺损中。结果表明，ASC 片与人工皮肤的联合移植加速了伤口愈合和血管生成，在治疗后 2 周观察到显著差异。ASC 片在体外大量分泌多种血管生成生长因子，并且在体内观察到移植的 ASC 位于血管周围区域并整合到新构建的血管结构中。这些结果表明，在这种糖尿病伤口愈合模型中，ASC 片直接和间接地加速了伤口愈合。总之，同种异体 ASC 片作为治疗糖尿病溃疡的新治疗策略具有潜力。
