Hu Yan-Hua, Wu De-Quan, Gao Feng, Li Guo-Dong, Yao Lei, Zhang Xin-Chen
Department of General Surgery, Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Hepatobiliary Pancreat Dis Int. 2009 Jun;8(3):255-60.
Mesenchymal stem cells derived from human umbilical cord blood (UCB-MSCs) have good research and application prospects in the treatment of diabetes. We once induced UCB-MSCs to differentiate into insulin-producing cells (IPCs) in vitro, but we did not know the functions of these cells in vivo. The aim of this study was to assess the functional effects of IPCs on insulin secretion and their role in the treatment of diabetes in vivo.
UCB-MSCs were induced to IPCs by an inducing protocol with extracellular matrix gel. BALB/C nude mice were made hyperglycemic by intraperitoneal injection of streptozotocin. The diabetic mice were transplanted with 1X10(7) IPCs under the renal capsule or with phosphate-buffered saline as a control. After transplantation, the grafts were analyzed by immunocytochemistry for the expression of human insulin; the serum human insulin levels were measured; and blood glucose and body weight status were monitored.
Immunofluorescence showed that numerous IPCs under the kidney capsule were insulin-positive. On day 14 after transplantation, the serum human insulin level of the treatment group (n=9) averaged 0.44+/-0.12 mU/L, which was higher than that of the control group (n=9) that did not express insulin (t=10.842, P<0.05). The diabetic mice remained hyperglycemic and kept losing body weight after IPC transplantation, and there was no significant difference in the control group.
IPCs differentiated from UCB-MSCs generate human insulin in diabetic mice, but more research is needed to make further use of them to regulate hyperglycemia and body weight in vivo.
源自人脐带血的间充质干细胞(UCB-MSCs)在糖尿病治疗方面具有良好的研究和应用前景。我们曾在体外诱导UCB-MSCs分化为胰岛素分泌细胞(IPCs),但尚不清楚这些细胞在体内的功能。本研究旨在评估IPCs对胰岛素分泌的功能影响及其在体内糖尿病治疗中的作用。
采用细胞外基质凝胶诱导方案将UCB-MSCs诱导为IPCs。通过腹腔注射链脲佐菌素使BALB/C裸鼠发生高血糖。将糖尿病小鼠在肾被膜下移植1×10⁷个IPCs,以磷酸盐缓冲盐水作为对照。移植后,通过免疫细胞化学分析移植物中人胰岛素的表达;测定血清人胰岛素水平;监测血糖和体重状况。
免疫荧光显示肾被膜下大量IPCs呈胰岛素阳性。移植后第14天,治疗组(n = 9)血清人胰岛素水平平均为0.44±0.12 mU/L,高于未表达胰岛素的对照组(n = 9)(t = 10.842,P < 0.05)。IPCs移植后糖尿病小鼠仍处于高血糖状态且体重持续减轻,对照组无显著差异。
UCB-MSCs分化而来的IPCs在糖尿病小鼠中可产生人胰岛素,但要进一步利用它们在体内调节高血糖和体重还需要更多研究。