同种异体脐带间充质干细胞移植治疗树鼩代谢综合征

Allogeneic umbilical cord mesenchymal stem cell transplantation for metabolic syndrome in a tree shrew model

背景:目前代谢综合征的治疗主要是改善生活和药物为主的综合性治疗,这些治疗要求患者有较强的随访性且不良反应多,尚不能从根本上改善、延缓代谢综合征发展。目的:探讨树鼩脐带间充质干细胞移植治疗树鼩代谢综合征的疗效,为临床应用干细胞移植治疗代谢综合征提供理论基础及参考方法。方法:实验采用贴壁培养法获得树鼩脐带间充质干细胞,鉴定其符合脐带间充质干细胞的生物学特性,深红色荧光碘化物DIR标记树鼩脐带间充质干细胞。32只树鼩给予高糖高胆固醇高盐饲料及糖水饮食,联合注射链脲佐菌素诱导代谢综合征模型,随机分为模型对照组(n=10)和脐带间充质干细胞治疗组(n=22)。治疗组树鼩经尾静脉注射体外标记的脐带间充质干细胞,模型对照组树鼩于同一时间注入等体积的生理盐水。移植后进行血液生化指标、葡萄糖耐量、胰岛素抵抗指数和动脉血压检测。结果与结论:①成功构建树鼩代谢综合征模型,表现出明显的胰岛素抵抗、高血糖、脂代谢紊乱、高血压,符合代谢综合征诊断标准;②脐带间充质干细胞移植能够显著降低代谢综合征树鼩血糖、血脂,改善胰岛素抵抗,调节胰岛素分泌;③移植的脐带间充质干细胞可归巢至代谢综合征树鼩肝脏、肾脏及胰腺组织内,并产生一定的修复作用。

BACKGROUND:Current treatments for metabolic syndrome are comprehensive treatments with drugs,aiming to improve patient’s life.Patients are required to have a high compliance to follow-up and have developed various adverse reactions.Therefore,there is no treatment to fundamentally delay the development of metabolic syndrome.OBJECTIVE:To establish a tree shrew model of metabolic syndrome and evaluation techniques,and to explore the therapeutic effect of umbilical cord mesenchymal stem cells in the tree shrew model,providing theoretical basis and reference method for clinical application of stem cell transplantation in metabolic syndromes.METHODS:Umbilical cord mesenchymal stem cells of tree shrews were obtained by adherent culture method,and met the biological characteristics of umbilical cord mesenchymal stem cells.The dark red fluorescent iodide DIR was used to label tree umbilical cord mesenchymal stem cells.Thirty-two tree shrews were fed high-sugar,high-cholesterol,high-salt diet and syrup diet,and injected streptozotocin to make metabolic syndrome models.Animal models were randomly divided into model control group(n=10)and cell treatment group(n=22).In the cell treatment group,the umbilical cord mesenchymal stem cells labeled in vitro were injected into the tail vein,and the model group was injected an equal volume of physiological saline in the meanwhile.Blood biochemical indicators,glucose tolerance,insulin resistance index and arterial blood pressure were measured after transplantation.RESULTS AND CONCLUSION:The tree shrew model of metabolic syndrome was successfully constructed,showing obvious insulin resistance,hyperglycemia,lipid metabolism disorder,and hypertension,which met the diagnostic criteria of metabolic syndrome.Umbilical cord mesenchymal stem cells transplantation could significantly reduce the blood glucose and blood lipid levels,improve insulin resistance and regulate insulin secretion in the tree shrew model of metabolic syndrome.Transplanted umbilical cord mesenchymal stem cells could be homing to the liver,kidney and pancreas of the tree shrew model of metabolic syndrome,and produce certain repairing effects.