SIAT-GHMSCB Biomedical Laboratory for Major Diseases, Dongguan Enlife Stem Cell Biotechnology Institute, Dongguan Avenue 430, Dongguan, Guangdong, China.
Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Blvd 1068, Shenzhen, Guangdong, China.
Stem Cell Res Ther. 2021 Jul 7;12(1):385. doi: 10.1186/s13287-021-02463-x.
The 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.
Fourteen-to-fifteen-week-old male C57BL/6 db/db mice 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.
UC-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.
Taken 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.
不同组织来源的间充质干细胞（MSCs）在代谢紊乱方面的治疗效果可能存在多种差异，但目前仍未得到明确界定。本研究报告了一项全面比较人脐带华通氏胶（UC-MSCs）、牙髓（PU-MSCs）和脂肪组织（AD-MSCs）来源的间充质干细胞对 2 型糖尿病小鼠糖脂代谢紊乱的治疗作用。
14-15 周龄雄性 C57BL/6 db/db 小鼠每周静脉注射不同剂量的人 UC-MSCs、PU-MSCs 和 AD-MSCs 或 vehicle 对照 1 次，共 6 周。另一组动物在第 4 至 6 周给予二甲双胍（MET）口服，每天 1 次作为阳性对照。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，采集血液和肝脏组织进行生化和组织学检查。
UC-MSCs 以剂量依赖性方式降低空腹血糖水平、增加空腹胰岛素水平、改善 GTT 和 ITT，效果最强，而 PU-MSCs 效果居中，AD-MSCs 效果最差。此外，UC-MSCs 还降低了血清低密度脂蛋白胆固醇（LDL-C）水平，效果最为显著，而 AD-MSCs 对 LDL-C 几乎没有影响。相反，AD-MSCs 显著降低了肝脏的脂质含量和组织损伤，以及伴随的肝损伤生物标志物如血清天冬氨酸转氨酶（AST）和丙氨酸氨基转移酶（ALT）水平，而 UC-MSCs 和 PU-MSCs 对这些参数分别没有或仅有适度影响。
综上所述，我们的研究结果表明，不同组织来源的间充质干细胞在改善 2 型糖尿病的糖脂代谢紊乱方面具有显著不同的治疗效果。在未来的临床实践中，可以根据治疗目的选择具有不同治疗特征的间充质干细胞。
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