Nature Biotechnology 23, 1274 - 1282 (2005)
Published online: 25 September 2005; | doi:10.1038/nbt1145
A human  -cell line for transplantation therapy to control type 1 diabetesMichiki Narushima1, Naoya Kobayashi1, Teru Okitsu2, Yoshihito Tanaka3, Shun-Ai Li4, Yong Chen1, Atsushi Miki1, Kimiaki Tanaka1, Shuhei Nakaji3, Kohji Takei4, Alejandro Soto Gutierrez1, Jorge David Rivas-Carrillo1, Nalu Navarro-Álvarez1, Hee-Sook Jun5, 6, Karen A Westerman7, Hirofumi Noguchi2, Jonathan R T Lakey8, Philippe Leboulch7, 9, Noriaki Tanaka1
& Ji-Won Yoon51
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. 2
Department of Transplant Surgery, Kyoto University Hospital, 54 Seigoin-Kawaracho, Sakyoku, Kyoto 606-8507, Japan. 3
Medical Products Department, Kuraray Medical Co. Ltd., 1621 Shakazu, Kurashiki, 710-8622, Japan. 4
Department of Neuroscience, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. 5
Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, 3333 Green Bay Road, North Chicago, Illinois 60064, USA. 6
Department of Biochemistry, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759, Korea. 7
Massachusetts Institute of Technology, Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA and Genetix Pharmaceuticals, 840 Memorial Drive, Cambridge, Massachusetts 02139, USA. 8
Human Pancreatic Islet Transplant Program, The University of Alberta, Alberta T2N 4N1, Canada. 9
Harvard Medical School and Division of Hematology, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Ji-Won Yoon ji-won.yoon@rosalindfranklin.edu or Naoya Kobayashi immortal@md.okayama-u.ac.jp A human pancreatic  -cell line that is functionally equivalent to primary -cells has not been available. We established a reversibly immortalized human -cell clone (NAKT-15) by transfection of primary human -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 -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.
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