Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

被引：60

作者：

Bruin, Jennifer E. ^{[1
]}

Saber, Nelly ^{[1
]}

Braun, Natalie ^{[1
]}

Fox, Jessica K. ^{[1
]}

Mojibian, Majid ^{[1
]}

Asadi, Ali ^{[1
]}

Drohan, Campbell ^{[1
]}

O'Dwyer, Shannon ^{[1
]}

Rosman-Balzer, Diana S. ^{[2
]}

Swiss, Victoria A. ^{[2
]}

Rezania, Alireza ^{[2
]}

Kieffer, Timothy J. ^{[1
,3
]}

机构：

[1] Univ British Columbia, Dept Cellular & Physiol Sci, Inst Life Sci, Lab Mol & Cellular Med, Vancouver, BC V6T 1Z3, Canada

[2] Janssen R&D LLC, BetaLog Venture, Raritan, NJ 08869 USA

[3] Univ British Columbia, Dept Surg, Vancouver, BC V6T 1Z3, Canada

来源：

STEM CELL REPORTS | 2015年 / 4卷 / 04期

基金：

加拿大健康研究院;

关键词：

INTENSIVE INSULIN THERAPY; HIGH-FAT DIET; ISLET TRANSPLANTATION; T-CELLS; ADIPOSE-TISSUE; ANIMAL-MODELS; SHORT-TERM; RESISTANCE; MICE; MELLITUS;

D O I：

10.1016/j.stemcr.2015.02.011

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

引用

页码：605 / 620

页数：16

共 40 条

[1] β-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia [J].

Biarnés, M ;

Montolio, M ;

Nacher, V ;

Raurell, M ;

Soler, J ;

Montanya, E .

DIABETES, 2002, 51 (01) :66-72

[2] Local inflammatory response around diffusion chambers containing xenografts - Nonspecific destruction of tissues and decreased local vascularization [J].

Brauker, J ;

Martinson, LA ;

Young, SK ;

Johnson, RC .

TRANSPLANTATION, 1996, 61 (12) :1671-1677

[3] Characterization of polyhormonal insulin-producing cells derived in vitro from human embryonic stem cells [J].

Bruin, Jennifer E. ;

Erener, Suheda ;

Vela, Javier ;

Hu, Xiaoke ;

Johnson, James D. ;

Kurata, Harley T. ;

Lynn, Francis C. ;

Piret, James M. ;

Asadi, Ali ;

Rezania, Alireza ;

Kieffer, Timothy J. .

STEM CELL RESEARCH, 2014, 12 (01) :194-208

[4] Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice [J].

Bruin, Jennifer E. ;

Rezania, Alireza ;

Xu, Jean ;

Narayan, Kavitha ;

Fox, Jessica K. ;

O'Neil, John J. ;

Kieffer, Timothy J. .

DIABETOLOGIA, 2013, 56 (09) :1987-1998

[5] β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes [J].

Butler, AE ;

Janson, J ;

Bonner-Weir, S ;

Ritzel, R ;

Rizza, RA ;

Butler, PC .

DIABETES, 2003, 52 (01) :102-110

[6] Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice [J].

Denroche, Heather C. ;

Quong, Whitney L. ;

Bruin, Jennifer E. ;

Tuduri, Eva ;

Asadi, Ali ;

Glavas, Maria M. ;

Fox, Jessica K. ;

Kieffer, Timothy J. .

DIABETES, 2013, 62 (08) :2738-2746

[7] Leptin Therapy Reverses Hyperglycemia in Mice With Streptozotocin-Induced Diabetes, Independent of Hepatic Leptin Signaling [J].

Denroche, Heather C. ;

Levi, Jasna ;

Wideman, Rhonda D. ;

Sequeira, Roveena M. ;

Huynh, Frank K. ;

Covey, Scott D. ;

Kieffer, Timothy J. .

DIABETES, 2011, 60 (05) :1414-1423

[8] Mechanisms of defective glucose-induced insulin release in human pancreatic islets transplanted to diabetic nude mice [J].

Eizirik, DL ;

Jansson, L ;

Flodstrom, M ;

Hellerstrom, C ;

Andersson, A .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (08) :2660-2663

[9] β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes:: A new analysis [J].

Ferrannini, E ;

Gastaldelli, A ;

Miyazaki, Y ;

Matsuda, M ;

Mari, A ;

DeFronzo, RA .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (01) :493-500

[10] Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters [J].

Feuerer, Markus ;

Herrero, Laura ;

Cipolletta, Daniela ;

Naaz, Afia ;

Wong, Jamie ;

Nayer, Ali ;

Lee, Jongsoon ;

Goldfine, Allison B. ;

Benoist, Christophe ;

Shoelson, Steven ;

Mathis, Diane .

NATURE MEDICINE, 2009, 15 (08) :930-U137

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