A human β-cell line for transplantation therapy to control type 1 diabetes
A human β-cell line for transplantation therapy to control type 1 diabetes
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DOI：
10.1038/nbt1145
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发表时间：
2005-10-01
影响因子：
46.9
通讯作者：
Yoon, JW
中科院分区：
文献类型：
--
作者：
Narushima, M;Kobayashi, N;Yoon, JW
一种在功能上等同于原代β细胞的人胰腺β细胞系一直未被获得。我们通过用含有猿猴病毒40大T抗原（SV40T）以及两侧带有成对loxP重组靶点的人端粒酶逆转录酶（hTERT）cDNA的逆转录病毒载体转染原代人β细胞，建立了一个可逆永生化的人β细胞克隆（NAKT - 15），这使得能够通过Cre重组酶删除SV40T和TERT。回复后的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，并且像正常人胰岛一样，能对葡萄糖作出反应而分泌胰岛素。将NAKT - 15细胞移植到链脲佐菌素诱导的糖尿病重症联合免疫缺陷小鼠体内，可在2周内使血糖得到完美控制；小鼠保持正常血糖水平超过30周。这种细胞系的建立是朝着通过移植潜在治愈糖尿病迈出的一步。
A human pancreatic b-cell line that is functionally equivalent to primary b-cells has not been available. We established a reversibly immortalized human b-cell clone ( NAKT-15) by transfection of primary human b-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 b-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.