title: A human beta-cell line for transplantation therapy to control type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Michiki
authors.initials: M
authors.lastname: Narushima
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Teru
authors.initials: T
authors.lastname: Okitsu
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shun-Ai
authors.initials: SA
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miki
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakaji
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
authors.forename: Alejandro Soto
authors.initials: AS
authors.lastname: Gutierrez
authors.forename: Jorge David
authors.initials: JD
authors.lastname: Rivas-Carrillo
authors.forename: Nalu
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
authors.forename: Karen A
authors.initials: KA
authors.lastname: Westerman
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: Philippe
authors.initials: P
authors.lastname: Leboulch
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Yoon
mesh_terms: 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