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

119 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
Pages (from-to)1274-1282
Number of pages9
JournalNature Biotechnology
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 1 2005

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'A human β-cell line for transplantation therapy to control type 1 diabetes'. Together they form a unique fingerprint.

  • Cite this

    Narushima, M., Kobayashi, N., Okitsu, T., Tanaka, Y., Li, S. A., Chen, Y., Miki, A., Tanaka, K., Nakaji, S., Takei, K., Gutierrez, A. S., Rivas-Carrillo, J. D., Navarro-Álvarez, N., Jun, H. S., Westerman, K. A., Noguchi, H., Lakey, J. R. T., Leboulch, P., Tanaka, N., & 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