College of Life Science, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
China Agricultural University, Beijng 100094, China.
Mol Ther. 2018 Aug 1;26(8):1921-1930. doi: 10.1016/j.ymthe.2018.06.013. Epub 2018 Jun 19.
To assess the potential therapeutic effects of adipose tissue-derived mesenchymal stem cells (ASCs) for the treatment of type 2 diabetes (T2D), we compared the phenotype and functionality of ASCs isolated from high-fat diet and streptozotocin (STZ)-induced T2D and the leptin receptor-deficient (db/db) mice with cells from healthy C57BL/6 mice. ASCs from T2D or db/db mice showed similar expression patterns of cellular markers and abilities to differentiate into adipocytes, osteoblasts, and chondrocytes. However, the rate of proliferation was reduced. ASCs from db/db mice secreted less hepatocyte growth factor (HGF). T2D mice receiving a single intravenous injection of T2D or db/db ASCs showed increased insulin sensitivity, reduced inflammation and fat content in adipose tissue and the liver and increased pancreatic β cell mass through 5 weeks post-infusion. Our data show that, although ASCs from T2D or db/db mice had inferior proliferative capacity compared to cells from healthy controls, improved insulin sensitivity and less β cell death was seen in T2D mice receiving mesenchymal stem cell (MSC) therapy. This study offers evidence that ASCs from diabetic donors have the potential to be used for cell therapy in the treatment of insulin resistance and T2D.
为了评估脂肪组织来源的间充质干细胞(ASCs)治疗 2 型糖尿病(T2D)的潜在治疗效果,我们比较了高脂肪饮食和链脲佐菌素(STZ)诱导的 T2D 以及瘦素受体缺陷(db/db)小鼠与健康 C57BL/6 小鼠来源的 ASC 的表型和功能。来自 T2D 或 db/db 小鼠的 ASC 表现出相似的细胞标志物表达模式和向脂肪细胞、成骨细胞和软骨细胞分化的能力。然而,增殖率降低。db/db 小鼠来源的 ASC 分泌的肝细胞生长因子(HGF)较少。接受单次静脉注射 T2D 或 db/db ASC 的 T2D 小鼠在输注后 5 周内表现出胰岛素敏感性增加、脂肪组织和肝脏炎症和脂肪含量减少以及胰岛β细胞质量增加。我们的数据表明,尽管与健康对照组相比,来自 T2D 或 db/db 小鼠的 ASC 增殖能力较差,但在接受间充质干细胞(MSC)治疗的 T2D 小鼠中,观察到胰岛素敏感性改善和更少的β细胞死亡。这项研究提供了证据表明,来自糖尿病供体的 ASC 有可能用于治疗胰岛素抵抗和 T2D 的细胞治疗。