Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
J Mol Histol. 2018 Aug;49(4):419-428. doi: 10.1007/s10735-018-9772-5. Epub 2018 Apr 19.
Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ). Serum and pancreatic insulin were measured, islet morphology and its vascularization were investigated. hUSCs highly expressed CD29, CD73, CD90 and CD146, and could differentiate into, at least, bone and fat in vitro. Transplantation of hUSCs into HD-STZ treated mice prolonged the median survival time and improved their blood glucose, and into those with MLD-STZ improved the glucose tolerance, islet morphology and increased the serum and pancreas insulin content. Furthermore, CD31 expression increased significantly in islets of BALB/c nude mice treated with hUSCs compared to those of un-transplanted MLD-STZ mice. hUSCs could improve the median survival time and glucose homeostasis in STZ-treated mice through promoting islet vascular regeneration and pancreatic beta-cell survival.
人尿源干细胞（hUSCs）是细胞治疗的一种潜在干细胞来源。然而，hUSCs 对 1 型糖尿病葡萄糖代谢调节的影响尚不清楚。因此，本研究旨在评估 hUSCs 是否对链脲佐菌素（STZ）诱导的糖尿病具有保护作用。hUSCs 采用特殊培养基提取和培养。采用流式细胞术分析检测细胞表面标志物。BALB/c 雄性裸鼠注射高剂量 STZ（HD-STZ）或多次低剂量 STZ（MLD-STZ）。检测血清和胰腺胰岛素，观察胰岛形态及其血管化。hUSCs 高表达 CD29、CD73、CD90 和 CD146，并且能够在体外分化为至少骨和脂肪。将 hUSCs 移植到 HD-STZ 处理的小鼠中可延长其中位生存时间并改善其血糖水平，移植到 MLD-STZ 处理的小鼠中可改善葡萄糖耐量、胰岛形态并增加血清和胰腺胰岛素含量。此外，与未移植 MLD-STZ 小鼠相比，hUSCs 处理的 BALB/c 裸鼠胰岛中 CD31 表达明显增加。hUSCs 可通过促进胰岛血管再生和胰腺β细胞存活来改善 STZ 处理的小鼠的中位生存时间和葡萄糖稳态。
