A human β-cell line for transplantation therapy to control type 1 diabetes

被引：107

作者：

Narushima, M

Kobayashi, N

Okitsu, T

Tanaka, Y

Li, SA

Chen, Y

Miki, A

Tanaka, K

Nakaji, S

Takei, K

Gutierrez, AS

Rivas-Carrillo, JD

Navarro-Alvarez, N

Jun, HS

Westerman, KA

Noguchi, H

Lakey, JRT

Leboulch, P

Tanaka, N

Yoon, JW

机构：

[1] Rosalind Franklin Comprehens Diabet Ctr, Chicago Med Sch, N Chicago, IL 60064 USA

[2] Okayama Univ, Grad Sch Med & Dent, Dept Surg, Okayama 7008558, Japan

[3] Kyoto Univ Hosp, Dept Transplant Surg, Sakyo Ku, Kyoto 6068507, Japan

[4] Kuraray Med Co Ltd, Dept Med Prod, Kurashiki, Okayama 7108622, Japan

[5] Okayama Univ, Grad Sch Med & Dent, Dept Neurosci, Okayama 7008558, Japan

[6] Chosun Univ, Sch Med, Dept Biochem, Kwangju 501759, South Korea

[7] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[8] Genetix Pharmaceut, Cambridge, MA 02139 USA

[9] Univ Alberta, Human Pancreat Islet Transplant Program, Calgary, AB T2N 4N1, Canada

[10] Harvard Univ, Sch Med, Boston, MA 02115 USA

[11] Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA

来源：

NATURE BIOTECHNOLOGY | 2005年 / 23卷 / 10期

关键词：

D O I：

10.1038/nbt1145

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：1274 / 1282

页数：9

共 41 条

[1] Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells [J].