The tissue origin of human mesenchymal stem cells dictates their therapeutic efficacy on glucose and lipid metabolic disorders in type II diabetic mice.
The tissue origin of human mesenchymal stem cells dictates their therapeutic efficacy on glucose and lipid metabolic disorders in type II diabetic mice.
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人间充质干细胞的组织来源决定了其对II型糖尿病小鼠糖脂代谢紊乱的治疗功效
DOI：
10.1186/s13287-021-02463-x
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发表时间：
2021-07-07
影响因子：
7.5
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Ma Y;Wang L;Yang S;Liu D;Zeng Y;Lin L;Qiu L;Lu J;Chang J;Li Z
背景不同组织来源的间充质干细胞（mesenchymal stem cells，MSCs）对代谢性疾病的治疗效果差异很大，但目前尚不清楚。在这里，我们报告了来自脐带华顿氏胶质（UC-MSC）、牙髓（PU-MSC）和脂肪组织（AD-MSC）的人MSCs对II型糖尿病小鼠中的糖和脂质代谢紊乱的治疗的综合比较。和各种剂量的AD-MSC或媒介物对照，每2周一次，持续6周。在第4至6周，每天一次向单独组中的动物经口给予二甲双胍（MET）作为阳性对照。每周测量体重、血糖和胰岛素水平。每2周进行一次葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）。所有动物在第6周处死，收集血液和肝组织进行生化和组织学检查。ResultsUC-MSCs表现出最强的功效，在降低空腹血糖水平，增加空腹胰岛素水平，并改善GTT和ITT的剂量依赖性的方式，而PU-MSCs表现出中等的功效和AD-MSCs表现出最少的功效对这些参数。此外，UC-MSCs还能显著降低血清低密度脂蛋白胆固醇（LDL-C）水平，而AD-MSCs对LDL-C的影响很弱。相比之下，AD-MSC大幅降低了肝脏的脂质含量和组织学病变以及伴随的肝损伤生物标志物，例如血清天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平，而UC-MSC和PU-MSC对这些参数没有显示或显示出适度的影响。分别。结论总而言之，我们的结果表明，不同组织来源的MSC在改善II型糖尿病中的葡萄糖和脂质代谢紊乱方面可赋予显著不同的治疗功效。在今后的临床实践中可根据治疗目的选择具有不同治疗特性的MSCs。
BackgroundThe therapeutic efficacy of mesenchymal stem cells (MSCs) of different tissue origins on metabolic disorders can be varied in many ways but remains poorly defined. Here we report a comprehensive comparison of human MSCs derived from umbilical cord Wharton’s jelly (UC-MSCs), dental pulp (PU-MSCs), and adipose tissue (AD-MSCs) on the treatment of glucose and lipid metabolic disorders in type II diabetic mice.MethodsFourteen-to-fifteen-week-old male C57BL/6db/dbmice were intravenously administered with human UC-MSCs, PU-MSCs, and AD-MSCs at various doses or vehicle control once every 2 weeks for 6 weeks. Metformin (MET) was given orally to animals in a separate group once a day at weeks 4 to 6 as a positive control. Body weight, blood glucose, and insulin levels were measured every week. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed every 2 weeks. All the animals were sacrificed at week 6 and the blood and liver tissues were collected for biochemical and histological examinations.ResultsUC-MSCs showed the strongest efficacy in reducing fasting glucose levels, increasing fasting insulin levels, and improving GTT and ITT in a dose-dependent manner, whereas PU-MSCs showed an intermediate efficacy and AD-MSCs showed the least efficacy on these parameters. Moreover, UC-MSCs also reduced the serum low-density lipoprotein cholesterol (LDL-C) levels with the most prominent potency and AD-MSCs had only very weak effect on LDL-C. In contrast, AD-MSCs substantially reduced the lipid content and histological lesion of liver and accompanying biomarkers of liver injury such as serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, whereas UC-MSCs and PU-MSCs displayed no or modest effects on these parameters, respectively.ConclusionsTaken together, our results demonstrated that MSCs of different tissue origins can confer substantially different therapeutic efficacy in ameliorating glucose and lipid metabolic disorders in type II diabetes. MSCs with different therapeutic characteristics could be selected according to the purpose of the treatment in the future clinical practice.
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影响因子：
6
作者：
Park YB;Ha CW;Lee CH;Yoon YC;Park YG
通讯作者：
Park YG
DOI：
10.1126/science.1247391
发表时间：
2014-08-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fox IJ;Daley GQ;Goldman SA;Huard J;Kamp TJ;Trucco M
通讯作者：
Trucco M
影响因子：
2.7
作者：
Hu, Jianxia;Wang, Yangang;Xu, Hongmei
通讯作者：
Xu, Hongmei
影响因子：
4.3
作者：
Chai, Ning-Li;Zhang, Xiao-Bin;Linghu, En-Qiang
通讯作者：
Linghu, En-Qiang
影响因子：
4.1
作者：
Nagamura-Inoue, Tokiko;He, Haiping
通讯作者：
He, Haiping