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

Abstract:

: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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

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 JR,Leboulch P,Tanaka N,Yoon JW

doi

10.1038/nbt1145

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

1274-82

issue

10

eissn

1087-0156

issn

1546-1696

pii

nbt1145

journal_volume

23

pub_type

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