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

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