Li Yanhua, Zhang Rui, Qiao Haifa, Zhang Heping, Wang Yunfang, Yuan Hongfeng, Liu Qinbin, Liu Daqing, Chen Lin, Pei Xuetao
Department of Stem Cells and Regenerative Medicine, Beijing Institute of Transfusion Medicine, Beijing, China.
J Cell Physiol. 2007 Apr;211(1):36-44. doi: 10.1002/jcp.20897.
Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). Recombinant adenoviral vector was used to deliver PDX-1 gene into hMSCs. After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. After the differentiated PDX-1+ hMSCs were transplanted into STZ-induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes.
胰岛细胞替代被认为是I型糖尿病的最佳治疗方法。然而，用于移植的人胰岛的可用性有限。在此，我们表明通过引入胰腺十二指肠同源盒-1（PDX-1），人骨髓间充质干细胞（hMSCs）可被诱导分化为功能性胰岛素分泌细胞。重组腺病毒载体用于将PDX-1基因导入hMSCs。用Ad-PDX-1感染后，hMSCs成功地被诱导分化为胰岛素分泌细胞。分化的PDX-1+ hMSCs表达多种胰岛细胞基因，包括神经源蛋白3（Ngn3）、胰岛素、GK、葡萄糖转运蛋白2（Glut2）和胰高血糖素，以弱葡萄糖调节方式产生和释放胰岛素/C肽。将分化的PDX-1+ hMSCs移植到链脲佐菌素诱导的糖尿病小鼠中后，2周内可实现血糖正常，并维持至少42天。这些发现证实了hMSCs模型系统作为富集人β细胞或其前体的潜在基础，以及糖尿病细胞替代治疗的可能来源。
