A human beta-cell line for transplantation therapy to control type 1 diabetes.
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.
Narushima
Michiki
M
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Kobayashi
Naoya
N
Okitsu
Teru
T
Tanaka
Yoshihito
Y
Li
Shun-Ai
SA
Chen
Yong
Y
Miki
Atsushi
A
Tanaka
Kimiaki
K
Nakaji
Shuhei
S
Takei
Kohji
K
Gutierrez
Alejandro Soto
AS
Rivas-Carrillo
Jorge David
JD
Navarro-Alvarez
Nalu
N
Jun
Hee-Sook
HS
Westerman
Karen A
KA
Noguchi
Hirofumi
H
Lakey
Jonathan R T
JR
Leboulch
Philippe
P
Tanaka
Noriaki
N
Yoon
Ji-Won
JW
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D024861:Genetic Enhancement / Q000379:methods; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome