Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing 100853, China.
Biochem Biophys Res Commun. 2013 Jul 5;436(3):418-23. doi: 10.1016/j.bbrc.2013.05.117. Epub 2013 Jun 11.
The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Single-dose mesenchymal stem cell (MSC) infusion ameliorates hyperglycemia but fails to restore normoglycemia in diabetic animals. We therefore hypothesized that multiple intravenous MSC infusions may reverse hyperglycemia in type 2 diabetes (T2D) rats. We administered serial allogenous bone-marrow derived MSC infusions (1 × 10(6)cells/infusion) via the tail vein once every 2 weeks to T2D rats, induced by high-fat diet and streptozocin (STZ) administration. Hyperglycemia decreased only transiently after a single infusion in early-phase (1 week) T2D rats, but approximated normal levels after at least three-time infusions. This normal blood level was maintained for at least 9 weeks. Serum concentrations of both insulin and C-peptide were dramatically increased after serial MSC infusions. Oral glucose tolerance tests revealed that glucose metabolism was significantly ameliorated. Immunofluorescence analysis of insulin/glucagon staining revealed the restoration of islet structure and number after multiple MSC treatments. When multiple-MSC treatment was initiated in late-phase (5 week) T2D rats, the results were slightly different. The results of this study suggested that a multiple-MSC infusion strategy offers a viable clinical option for T2D patients.
全球范围内糖尿病的迅速增加对当前的治疗方法提出了重大挑战。单次间充质干细胞（MSC）输注可改善高血糖，但不能使糖尿病动物恢复正常血糖水平。因此，我们假设多次静脉内 MSC 输注可能逆转 2 型糖尿病（T2D）大鼠的高血糖。我们通过尾静脉每 2 周一次向高脂肪饮食和链脲佐菌素（STZ）给药诱导的 T2D 大鼠输注连续同种异体骨髓来源的 MSC（1×10(6)细胞/输注）。单次输注后，早期（1 周）T2D 大鼠的高血糖仅短暂下降，但至少 3 次输注后接近正常水平。这种正常的血液水平至少维持 9 周。血清胰岛素和 C 肽浓度在连续 MSC 输注后显著增加。口服葡萄糖耐量试验显示葡萄糖代谢明显改善。胰岛素/胰高血糖素染色的免疫荧光分析显示，多次 MSC 治疗后胰岛结构和数量得到恢复。当在晚期（5 周）T2D 大鼠中开始多次-MSC 治疗时，结果略有不同。这项研究的结果表明，多次-MSC 输注策略为 T2D 患者提供了一种可行的临床选择。
