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

Nat Biotechnol. 2005 Oct;23(10):1274-82. doi: 10.1038/nbt1145. Epub 2005 Sep 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods*
  • Cell Line
  • Cell Proliferation
  • Diabetes Mellitus, Type 1 / surgery*
  • Genetic Enhancement / methods
  • Humans
  • Islets of Langerhans / physiology*
  • Islets of Langerhans Transplantation / methods*
  • Mice
  • Mice, SCID
  • Tissue Engineering / methods*
  • Treatment Outcome