模拟糖尿病创面微环境预处理人iPSC-MSCs的外泌体优化方案探讨及关键效应microRNA筛选

糖尿病慢性创面是临床医学丞待解决难题，MSCs是治疗糖尿病创面极具临床前景且已进入临床试验的重要手段。但MSCs产业化存在缺陷及临床应用潜在的风险是其不足。近来MSCs旁分泌的外泌体被认为是具有与MSCs等效生物效应又规避其潜在临床风险，未来可能替代MSCs的研究方向。但MSCs旁分泌的外泌体与MSCs感受到的病理性微环境状况密切相关。现行脱离治疗疾病病理特征的分离提取外泌体方法显然存在明显科学问题。本研究将采用目前产业化前景较好的iPSC-MSCs为研究对象，并尽可能模拟糖尿病创面微环境特有病理状况，采用不同因素组合，在体内外探讨糖尿病创面治疗的MSCs外泌体优化预处理方案，并进一步探讨优化方案中治疗糖尿病创面关键miRNA，有望为治疗糖尿病创面甚至其他疾病的MSCs外泌体关键miRNA的寻找及进一步针对性的关键miRNA加载治疗提供新的研究思路与方向。

Diabetic chronic wounds are difficult problems to be solved in clinic. Mesenchymal Stem Cell transplantation is an important method in the treatment of diabetic chronic wounds with favorable clinical prospects. But the Mesenchymal Stem Cell transplantation treatment has several shortcomings such as the deficiency of Industrial production and the potential risk of clinical application. Recently, it has been found that exosomes not only have the same biological effects as stem cells, but can also avoid those risks and have been regarded as a priority treatment instead of mesenchymal stem cell transplantation in the future. But the factors in disease microenvironment can affect the exosome secretion of mesenchymal stem cells. Isolated exosomes away from the disease microenvironment would not mimic the true situation. This study will use the iPSC-MSCs, which has good prospect of industrialization, to explore the treatment of diabetic wound with exosomes after pre-stimulation with homogenate from diabetic wounds and different combinations of stimuli in vivo and in vitro, and further explore the key miRNA of iPSC-MSCs-Exos. It is expected to provide new research ideas and directions for the search of key miRNA of MSCs exosomes in the treatment of diabetic wounds and even other diseases and the further targeted treatment of key miRNA loading.