A human beta-cell line for transplantation therapy to control type 1 diabetes.
A human beta-cell line for transplantation therapy to control type 1 diabetes.
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发表时间：
2005
影响因子：
46.9
通讯作者：
M. Narushima;N. Kobayashi;T. Okitsu;Yoshihito Tanaka;Shun‐Ai Li;Yong Chen;A. Miki;Kimiaki Tanaka-Kimiaki-Tan
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作者：
M. Narushima;N. Kobayashi;T. Okitsu;Yoshihito Tanaka;Shun‐Ai Li;Yong Chen;A. Miki;Kimiaki Tanaka-Kimiaki-Tan
尚未获得功能上等同于原代β细胞的人胰腺β细胞系。我们通过用逆转录病毒载体转染原代人β细胞建立了可逆永生化的人β细胞克隆（NAKT-15），所述逆转录病毒载体含有侧接配对loxP重组靶的猿猴病毒40大T抗原（SV 40 T）和人端粒酶逆转录酶（hTERT）cDNA，其允许通过Cre重组酶缺失SV 40 T和TERT。回复的NAKT-15细胞表达β细胞转录因子（Isl-1、Pax 6、Nkx 6.1、Pdx-1）、激素原转化酶1/3和2以及分泌颗粒蛋白，并响应于葡萄糖而分泌胰岛素，类似于正常人胰岛。将NAKT-15细胞移植到链脲佐菌素诱导的糖尿病重度联合免疫缺陷小鼠中，在2周内血糖得到完美控制;小鼠保持正常血糖超过30周。该细胞系的建立是通过移植治疗糖尿病的潜在方法的一步。
A human pancreatic beta-cell line that is functionally equivalent to primary beta-cells has not been available. We established a reversibly immortalized human beta-cell clone (NAKT-15) by transfection of primary human beta-cells with a retroviral vector containing simian virus 40 large T-antigen (SV40T) and human telomerase reverse transcriptase (hTERT) cDNAs flanked by paired loxP recombination targets, which allow deletion of SV40T and TERT by Cre recombinase. Reverted NAKT-15 cells expressed beta-cell transcription factors (Isl-1, Pax 6, Nkx 6.1, Pdx-1), prohormone convertases 1/3 and 2, and secretory granule proteins, and secreted insulin in response to glucose, similar to normal human islets. Transplantation of NAKT-15 cells into streptozotocin-induced diabetic severe combined immunodeficiency mice resulted in perfect control of blood glucose within 2 weeks; mice remained normoglycemic for longer than 30 weeks. The establishment of this cell line is one step toward a potential cure of diabetes by transplantation.