应用富血小板血浆在内皮祖细胞移植促进糖尿病创面愈合中的作用和机制

Diabetic wound, as a kind of refractory wound, is very difficult to heal. Both Endothelial progenitor cells transplantation and platelet-rich plasma could improve diabetic wound healing to some extent. But because of shortage and dysfunction of reparative cells and shortage of many growth factors in diabetic wound tissues, either of them alone cannot get a very satisfactory result for some patients. PRP application cannot provide reparative cells for wound and EPCs transplantation cannot replenish the required growth factors. furthermore, the proliferation, differentiation and fate of the transplanted EPCs are not known very well. For these reasons, we decide to combine PRP application with EPCs transplantation to improve diabetic wound healing. PRP application could provide the necessary growth factors for wound and EPCs transplantation, which could offer the required cells in return. In addition, Notch signling pathway plays a key role in regulation of proliferation and differentiation of stem cells and angiogenesis in wound. Hence, the effect of PRP application on biological functions and fate of EPCs will be investigated in this study, and the role of PRP in enhancing the therapeutic results of improving diabetic wound healing by EPCs transplantation and its role in changing the status of Notch signling pathway will be observed. At the same time, the possible mechanism of the combination treatment for diabetic wound healing will be explored on morphological, histological, molecular biological and genetic level. This study will provide a novel way to treat diabetic wound more efficiently and improve the therapeutic effect of the EPCs transplantation.

糖尿病(DM)创面为难愈性创面，治疗困难。内皮祖细胞(EPCs)移植和富血小板血浆(PRP)均可促进其愈合。但DM创面内修复性细胞缺乏及功能异常，多种生长因子不足，单独应用PRP无法补充其缺乏的修复细胞，EPCs移植不能解决生长因子缺乏的问题，且其移植后的增殖分化和转归尚不明确。基于此，本实验将PRP与EPCs移植相结合，用以促进DM创面愈合，使其互为补充，EPCs移植为血管新生提供细胞源，PRP补充细胞增殖分化及创面愈合所需的多种因子；另外，Notch信号通路对于调控干细胞增殖分化和血管新生具有重要作用；为此，本实验将检测PRP对EPCs生物学功能和移植后转归的影响，观察其增强EPCs移植促进DM创面愈合的作用，探讨Notch信号通路状态在应用PRP后的改变及其作用，从形态学、组织学、分子生物学和基因水平探讨相关的机制。本研究将为治疗DM创面和增强EPCs移植的效果找到有效的新方法。

糖尿病（DB）创面为难愈性创面，治疗困难。内皮祖细胞（EPCs）移植和富血小板血浆（PRP）均可促进其愈合。但DB创面内修复性细胞缺乏及功能异常，多种生长因子不足，单独应用PRP无法补充其缺乏的修复细胞，EPCs移植不能解决生长因子缺乏的问题，且其移植后的增殖分化和转归尚不明确。基于此，本实验将PRP与EPCs移植相结合，用以促进DM创面愈合，使其互为补充，EPCs移植为血管新生提供细胞源，PRP补充细胞增殖分化及创面愈合所需的多种因子；另外，Notch信号通路对于调控干细胞增殖分化和血管新生具有重要作用；为此，本实验将检测PRP对EPCs生物学功能和移植后转归的影响，观察其增强EPCs移植促进DM创面愈合的作用，探讨Notch信号通路状态在应用PRP后的改变及其作用，从形态学、组织学、分子生物学和基因水平探讨相关的机制。本研究将为治疗DM创面和增强EPCs移植的效果找到有效的新方法。