摘要
背景:间充质干细胞治疗急性心肌梗死的机制与间充质干细胞的迁移、定植和分化相关,更重要的是间充质干细胞的旁分泌作用。目的:评估低氧体积分数下脂肪间充质干细胞和脐带间充质干细胞的旁分泌及促血管再生能力,为选择合适的间充质干细胞应用于治疗急性心肌梗死提供依据。方法:分离并培养人脂肪间充质干细胞和人脐带间充质干细胞,流式细胞术鉴定细胞的免疫表型;2种细胞按氧体积分数不同各分为体积分数3%O_2预处理组、体积分数5%O_2预处理组和体积分数21%O_2对照组,培养24 h;酶联免疫吸附法检测各组细胞上清液肝细胞生长因子、血管内皮生长因子、神经生长因子、角质细胞生长因子水平。结果与结论:(1)2种间充质干细胞阳性表达CD73、CD90、CD105,阴性表达CD34、CD45、CD54、HLA-DR;(2)各氧体积分数条件下,人脂肪间充质干细胞分泌血管内皮生长因子水平均显著高于人脐带间充质干细胞(P<0.01);(3)在体积分数5%O_2条件下,人脂肪间充质干细胞分泌肝细胞生长因子水平显著高人脐带间充质干细胞(P<0.05);(4)在体积分数3%O_2和体积分数5%O_2条件下,人脐带间充质干细胞分泌神经生长因子水平显著高于人脂肪间充质干细胞(P<0.01);(5)在体积分数3%O_2和体积分数5%O_2条件下,人脐带间充质干细胞分泌角质细胞生长因子水平显著高于人脂肪间充质干细胞(P<0.01或P<0.05),在体积分数21%O_2条件下,人脂肪间充质干细胞分泌角质细胞生长因子水平显著高于人脐带间充质干细胞(P<0.01);(6)结果表明,低氧能够提高2种干细胞旁分泌效应。人脂肪间充质干细胞在血管内皮生长因子旁分泌能力上明显优于人脐带间充质干细胞,故认为人脂肪间充质干细胞可能更适合用于心肌梗死的干细胞治疗。
BACKGROUND: Therapeutic mechanisms of mesenchymal stem cells for acute myocardial infarction are related to the migration, colonization, and differentiation of mesenchymal stem cells, and more importantly, it is related to the paracrine effects of mesenchymal stem cells.OBJECTIVE: To evaluate the paracrine and vascular regeneration abilities of human adipose-derived mesenchymal stem cells (hAD-MSCs) and human umbilical cord mesenchymal stem cells (hUC-MSCs) under low oxygen concentrations, thereby providing the basis for the selection of appropriate mesenchymal stem cells used in the treatment of acute myocardial infarction.METHODS: hUC-MSCs and hAD-MSCs were isolated and cultured, and cell immunophenotype was identified using flow cytometry. Two kinds of cells were pretreated with 3%, 5% and 21% (control) O2 for 24 hours. Enzyme linked immunosorbent assay was used to detect the contents of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and keratinocyte growth factor (KGF) in the cell supernatant in each group.RESULTS AND CONCLUSION: hUC-MSCs and hAD-MSCs were positive for CD73, CD90 and CD105, and negative for CD34, CD45, CD54 and HLA-DR. Under different oxygen concentrations, the VEGF level in the hAD-MSCs was significantly higher than that in the hUC-MSCs (P 〈 0.01). Under 3% O2 conditions, the HGF level in the hAD-MSCs was significantly higher than that in the hUC-MSCs (P 〈 0.05). Under 3% and 5% O2, the NGF level in the hUC-MSCs was significantly higher than that in the hAD-MSCs (P 〈 0.01). Under 3% and 5% O2, the KGF level in the hUC-MSCs was significantly higher than that in the hAD-MSCs (P 〈 0.01 or P 〈 0.05). Under 21% O2, the KGF level in the hAD-MSCs was significantly higher than that in the hUC-MSCs (P 〈 0.01). To conclude, hypoxia can promote the paracrine effects of and hAD-MSCs. Moreover, hUC-MSCs show better paracrine ability than hAD-MSCs. Therefore, hAD-MSCs are more likely
作者
杨记农
姜亦瑶
袁超
刘志刚
刘晓程
Yang Ji-nong;Jiang Yi-yao;Yuan Chao;Liu Zhi-gang;Liu Xiao-cheng(Department of Cardiac Surgery,TEDA International Cardiovascular Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin 300457,China;Department of Cardiac Surgery,First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,Anhui Province,China;Nankai University,Tianjin 300071,China)
出处
《中国组织工程研究》
CAS
北大核心
2018年第21期3322-3327,共6页
Chinese Journal of Tissue Engineering Research
基金
天津市滨海新区卫生局基金项目(2014BHKY010)
天津市企业博士后创新项目择优资助计划(2015-001)
安徽省高校优秀青年人才支持计划重点项目(GXYQZD2016167)