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

Michiki Narushima, Naoya Kobayashi, Teru Okitsu, Yoshihito Tanaka, Shun Ai Li, Yong Chen, Atsushi Miki, Kimiaki Tanaka, Shuhei Nakaji, Kohji Takei, Alejandro Soto Gutierrez, Jorge David Rivas-Carrillo, Nalu Navarro-Álvarez, Hee Sook Jun, Karen A. Westerman, Hirofumi Noguchi, Jonathan R T Lakey, Philippe Leboulch, Noriaki Tanaka, Ji Won Yoon

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

A human pancreatic β-cell line that is functionally equivalent to primary β-cells has not been available. We established a reversibly immortalized human β-cell clone (NAKT-15) by transfection of primary human β-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 β-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.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalNature Biotechnology
Volume23
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Viral Tumor Antigens
Cell Transplantation
Antigens
Medical problems
Type 1 Diabetes Mellitus
Viruses
Glucose
Clone cells
Proprotein Convertase 1
Cells
Cell Line
Transcription factors
Insulin
Streptozocin
Simian virus 40
Blood Glucose
Blood
Transcription Factors
Complementary DNA
Proteins

ASJC Scopus subject areas

  • Microbiology

Cite this

Narushima, M., Kobayashi, N., Okitsu, T., Tanaka, Y., Li, S. A., Chen, Y., ... Yoon, J. W. (2005). A human β-cell line for transplantation therapy to control type 1 diabetes. Nature Biotechnology, 23(10), 1274-1282. https://doi.org/10.1038/nbt1145

A human β-cell line for transplantation therapy to control type 1 diabetes. / Narushima, Michiki; Kobayashi, Naoya; Okitsu, Teru; Tanaka, Yoshihito; Li, Shun Ai; Chen, Yong; Miki, Atsushi; Tanaka, Kimiaki; Nakaji, Shuhei; Takei, Kohji; Gutierrez, Alejandro Soto; Rivas-Carrillo, Jorge David; Navarro-Álvarez, Nalu; Jun, Hee Sook; Westerman, Karen A.; Noguchi, Hirofumi; Lakey, Jonathan R T; Leboulch, Philippe; Tanaka, Noriaki; Yoon, Ji Won.

In: Nature Biotechnology, Vol. 23, No. 10, 10.2005, p. 1274-1282.

Research output: Contribution to journalArticle

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-Álvarez, N, Jun, HS, Westerman, KA, Noguchi, H, Lakey, JRT, Leboulch, P, Tanaka, N & Yoon, JW 2005, 'A human β-cell line for transplantation therapy to control type 1 diabetes', Nature Biotechnology, vol. 23, no. 10, pp. 1274-1282. https://doi.org/10.1038/nbt1145
Narushima M, Kobayashi N, Okitsu T, Tanaka Y, Li SA, Chen Y et al. A human β-cell line for transplantation therapy to control type 1 diabetes. Nature Biotechnology. 2005 Oct;23(10):1274-1282. https://doi.org/10.1038/nbt1145
Narushima, Michiki ; Kobayashi, Naoya ; Okitsu, Teru ; Tanaka, Yoshihito ; Li, Shun Ai ; Chen, Yong ; Miki, Atsushi ; Tanaka, Kimiaki ; Nakaji, Shuhei ; Takei, Kohji ; Gutierrez, Alejandro Soto ; Rivas-Carrillo, Jorge David ; Navarro-Álvarez, Nalu ; Jun, Hee Sook ; Westerman, Karen A. ; Noguchi, Hirofumi ; Lakey, Jonathan R T ; Leboulch, Philippe ; Tanaka, Noriaki ; Yoon, Ji Won. / A human β-cell line for transplantation therapy to control type 1 diabetes. In: Nature Biotechnology. 2005 ; Vol. 23, No. 10. pp. 1274-1282.
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