诱导多能干细胞分化的平滑肌细胞促进糖尿病鼠创面愈合的研究  

Induced pluripotent stem cell-derived smooth muscle cells improve wound healing in diabetic mice

作　　者：高喜翔[1] 高明杰[2] 谷涌泉[1] 郭连瑞[1] GAO Xixiang;GAO Mingjie;GU Yongquan;GUO Lianrui(Department of Vascular Surgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Ultrasound,Luhe Hospital,Capital Medical University,Beijing 101199)

机构地区：[1]首都医科大学宣武医院血管外科,首都医科大学血管外科研究所,北京100053 [2]首都医科大学附属潞河医院超声科,北京101199

出　　处：《中国实验动物学报》2023年第7期880-887,共8页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家重点研发计划(2022YFC3602400,2022YFC3602404,2021YFC2500500,2021YFC2500504)。

摘　　要：目的研究人多能干细胞分化的平滑肌细胞(human pluripotent stem cell-derived smooth muscle cells,hiPSC-SMC)促进糖尿病裸鼠创面愈合的能力。方法将hiPSC-SMC、阳性对照脂肪来源干细胞(adipose-derived stem cells,ADSC)和阴性对照不含细胞的磷酸盐缓冲盐水(PBS)分别加入I型鼠尾胶原蛋白中制成干细胞胶原蛋白膜片或无细胞胶原蛋白膜片。在糖尿病裸鼠背部制作皮肤全层缺损的夹板创面模型。将制备的胶原蛋白膜片固定于创面上,在不同时间点对创面进行拍照、取材,并进行免疫组化染色和蛋白质印迹分析。结果hiPSC-SMC具有和ADSC一致的促进糖尿病裸鼠创面愈合的能力,创面在术后第2天即可表现出明显的缩小。hiPSC-SMC和ADSC组的创面与无细胞对照组相比,细胞增殖明显增多,α-SMA阳性细胞、CD31阳性细胞和VEGF-A阳性细胞均明显增多,VEGF-A和PDGF表达明显升高。结论hiPSC-SMC可以促进血管新生和再生细胞因子的表达,促进血管新生和细胞增殖,从而促进糖尿病裸鼠全层皮肤缺损的夹板创面的愈合。Objective To study the ability of human pluripotent stem cell-derived smooth muscle cells(hiPSC-SMCs)to improve wound healing in diabetic mice.Methods hiPSC-SMCs,positive control adipose-derived stem cells(ADSCs),and negative control cell-free phosphate-buffered saline(PBS)were added to type I rat tail collagen to prepare stem cell or cell-free collagen scaffolds.The scaffolds were applied to splinted back wounds in diabetic nude mice.The wound was photographed and harvested at various time points,and immunohistochemical staining and western blot analysis were performed.Results Compared with the cell-free control group,hiPSC-SMCs had the same ability as ADSCs to promote wound healing in diabetic mice.The wound size was significantly reduced the day after surgery.Wounds in hiPSC-SMC and ADSC groups had significantly more cell proliferation,α-SMA-positive cells,CD31-positive cells,VEGF-A-positive cells,and VEGF-A and PDGF expression.Conclusions hiPSC-SMCs promote the expression of angiogenic and regenerative cytokines,and promote angiogenesis and cell proliferation,thereby promoting wound healing in diabetic mice.

关 键 词：干细胞 人多能干细胞 脂肪来源干细胞 平滑肌细胞 糖尿病足 慢性创面 创面愈合 血管新生 

分 类 号：Q95-33[生物学—动物学]