Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice
Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice
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DOI：
10.1387/ijdb.092953hk
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发表时间：
2010-01-01
影响因子：
0.7
通讯作者：
Asashima, Makoto
中科院分区：
文献类型：
--
作者：
Kajiyama, Hiromitsu;Hamazaki, Tatsuo S.;Asashima, Makoto
胰岛素依赖型糖尿病（IDDM）的特征是由于胰岛素缺乏导致的潜在严重代谢异常的快速发展。胰岛素分泌细胞移植是治疗胰岛素依赖型糖尿病的一种有前途的方法。转录因子胰腺十二指肠同源框1（Pdx 1）在胰腺β细胞的分化中起重要作用。在这项研究中，人Pdx 1基因转导和表达在小鼠脂肪组织来源的干细胞（ASCs）。为了评估胰腺修复，我们使用了导致高血糖症的胰腺损伤的小鼠模型，该模型涉及向小鼠注射链脲佐菌素（STZ）。与对照小鼠相比，STZ处理的移植有Pdx 1转导的ASCs（Pdx 1-ASCs）的小鼠显示出显著降低的血糖水平和增加的存活率。虽然在我们的实验中，Pdx 1在ASC中的稳定表达在体外没有诱导胰腺表型，但移植的干细胞在胰腺中植入，其中它们表达胰岛素和C肽，这是胰岛素产生细胞的标志物。这些结果表明，Pdx 1-ASC在胰腺中稳定地移植，获得功能性β细胞表型，并在体内部分恢复胰腺功能。从脂肪组织中提取大量细胞的简便性和安全性支持了该系统开发用于IDDM的新细胞疗法的适用性。
Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. In this study, the human Pdx1 gene was transduced and expressed in murine adipose tissue-derived stem cells (ASCs). To evaluate pancreatic repair, we used a mouse model of pancreatic damage resulting in hyperglycemia, which involves injection of mice with streptozotocin (STZ). STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. These results suggest that Pdx1-ASCs are stably engrafted in the pancreas, acquire a functional beta-cell phenotype, and partially restore pancreatic function in vivo. The ease and safety associated with extirpating high numbers of cells from adipose tissues support the applicability of this system to developing a new cell therapy for IDDM.