期刊
DIABETES
卷 67, 期 1, 页码 26-35出版社
AMER DIABETES ASSOC
DOI: 10.2337/db17-0120
关键词
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资金
- Russell Berrie Foundation Program in Cellular Therapies for Diabetes
- New York State Stem Cell Science (NYSTEM) IDEA award [C029552]
- Leona and Harry Helmsley Charitable Trust [2015PG-T1D069]
- Human Islet Research Network [UC4-DK-104207]
- National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIH) [RO1-DK-103585]
- American Diabetes Association [7-11-MN-62]
- JDRF Microfluidic-Based Functional Facility at University of Illinois Chicago under NIH [R01-DK-091526]
- Chicago Diabetes Project
- New York Stem Cell Foundation
- NIH [DK-72473, DK-89572, DK-104211, DK-106755]
- JDRF
- Department of Veterans Affairs
- Vanderbilt Diabetes Research and Training Center [DK-20593]
- Diabetes and Endocrinology Research Center [5P30-DK-063608]
- Office of the Director, NIH [S10-RR-027050, S10-OD-020056]
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR027050] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK020593, U01DK089572, P30DK063608, R24DK106755, U01DK072473, UC4DK104211, R01DK091526, T32DK007563, R01DK103585, P60DK020593, UC4DK104207, P30DK026687] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD020056] Funding Source: NIH RePORTER
beta-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into beta-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These beta-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-beta-cells maintain normal blood glucose levels after ablation of the mouse endogenous beta-cells. Cystic structures, but no teratomas, were observed in NT-ES-beta-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in beta-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-beta-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy.
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