Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic β-like cells

被引:176
作者
Alipio, Zaida [2 ]
Liao, Wenbin [3 ]
Roemer, Elizabeth J. [3 ]
Waner, Milton [4 ]
Fink, Louis M. [2 ]
Ward, David C. [1 ]
Ma, Yupo [3 ]
机构
[1] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA
[2] Nevada Canc Inst, Div Lab Med, Las Vegas, NV 89135 USA
[3] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA
[4] Vasc & Birthmark Inst New York, New York, NY 10023 USA
关键词
cellular therapy; diabetes; stem cells; somatic cell programming; INSULIN-PRODUCING CELLS; DEFINED FACTORS; MOLECULAR PHYSIOLOGY; SOMATIC-CELLS; THERAPY; DIFFERENTIATION; TRANSPLANTATION; GENERATION; INDUCTION; ISLETS;
D O I
10.1073/pnas.1007884107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Diabetes mellitus is characterized by either the inability to produce insulin (type 1 diabetes) or as insensitivity to insulin secreted by the body (type 2 diabetes). In either case, the body is unable to move blood glucose efficiently across cell membranes to be used. This leads to a variety of local and systemic detrimental effects. Current treatments for diabetes focus on exogenous insulin administration and dietary control. Here, we describe a potential cure for diabetes using a cellular therapy to ameliorate symptoms associated with both reduced insulin secretion and insulin sensitivity. Using induced pluripotent stem (iPS) cells, we were able to derive beta-like cells similar to the endogenous insulin-secreting cells in mice. These beta-like cells secreted insulin in response to glucose and corrected a hyperglycemic phenotype in two mouse models of type 1 and 2 diabetes via an iPS cell transplant. Long-term correction of hyperglycemia was achieved, as determined by blood glucose and hemoglobin A1c levels. These data provide an initial proof of principle for potential clinical applications of reprogrammed somatic cells in the treatment of diabetes type 1 or 2.
引用
收藏
页码:13426 / 13431
页数:6
相关论文
共 23 条
[1]   Embryonic stem cell therapy for diabetes mellitus [J].
Docherty, Kevin ;
Bernardo, Andreia S. ;
Vallier, Ludovic .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2007, 18 (06) :827-838
[2]  
Gu GQ, 2002, DEVELOPMENT, V129, P2447
[3]   Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin [J].
Hanna, Jacob ;
Wernig, Marius ;
Markoulaki, Styliani ;
Sun, Chiao-Wang ;
Meissner, Alexander ;
Cassady, John P. ;
Beard, Caroline ;
Brambrink, Tobias ;
Wu, Li-Chen ;
Townes, Tim M. ;
Jaenisch, Rudolf .
SCIENCE, 2007, 318 (5858) :1920-1923
[4]   MOLECULAR PHYSIOLOGY OF THE ISLET AMYLOID POLYPEPTIDE (IAPP)/AMYLIN GENE IN MAN, RAT, AND TRANSGENIC MICE [J].
HOPPENER, JWM ;
OOSTERWIJK, C ;
VANHULST, KL ;
VERBEEK, JS ;
CAPEL, PJA ;
DEKONING, EJP ;
CLARK, A ;
JANSZ, HS ;
LIPS, CJM .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1994, 55 :39-53
[5]   Cell-based treatments for diabetes [J].
Jones, Peter M. ;
Courtney, Monica L. ;
Burns, Christopher J. ;
Persaud, Shanta J. .
DRUG DISCOVERY TODAY, 2008, 13 (19-20) :888-893
[6]   Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation [J].
Karnieli, Ohad ;
Izhar-Prato, Yael ;
Bulvik, Shlomo ;
Efrat, Shimon .
STEM CELLS, 2007, 25 (11) :2837-2844
[7]   TRANSPLANTATION OF ISOLATED PANCREATIC-ISLETS INTO PORTAL VEIN OF DIABETIC RATS [J].
KEMP, CB ;
KNIGHT, MJ ;
SCHARP, DW ;
LACY, PE ;
BALLINGER, WF .
NATURE, 1973, 244 (5416) :447-447
[8]   Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo [J].
Kroon, Evert ;
Martinson, Laura A. ;
Kadoya, Kuniko ;
Bang, Anne G. ;
Kelly, Olivia G. ;
Eliazer, Susan ;
Young, Holly ;
Richardson, Mike ;
Smart, Nora G. ;
Cunningham, Justine ;
Agulnick, Alan D. ;
D'Amour, Kevin A. ;
Carpenter, Melissa K. ;
Baetge, Emmanuel E. .
NATURE BIOTECHNOLOGY, 2008, 26 (04) :443-452
[9]  
Lakey JRT, 2006, METH MOL B, V333, P47
[10]   Reprogramming somatic cells towards pluripotency by defined factors [J].
Lewitzky, Marc ;
Yamanaka, Shinya .
CURRENT OPINION IN BIOTECHNOLOGY, 2007, 18 (05) :467-473