Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

Abstract

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.

• Authors: Jennifer E Bruin, Nelly Saber, Natalie Braun, Jessica K Fox, Majid Mojibian, Ali Asadi, Campbell Drohan, Shannon O'Dwyer, Diana S Rosman-Balzer, Victoria A Swiss, Alireza Rezania, Timothy J Kieffer
• Journal: Stem cell reports (Stem Cell Reports) Vol. 4 Issue 4 Pg. 605-20 (Apr 14 2015) ISSN: 2213-6711 [Electronic] United States
• PMID: 25801507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Hypoglycemic Agents
• Glucose

Topics

• Animals
• Cell Differentiation
• Cell- and Tissue-Based Therapy
• Diabetes Mellitus, Type 2 (etiology, metabolism, therapy)
• Diet (adverse effects)
• Diet, High-Fat (adverse effects)
• Disease Models, Animal
• Gene Expression Profiling
• Glucose (metabolism)
• Human Embryonic Stem Cells (cytology)
• Humans
• Hyperglycemia
• Hypoglycemic Agents (pharmacology)
• Insulin Resistance
• Insulin-Secreting Cells (cytology, metabolism)
• Islets of Langerhans (cytology)
• Liver (anatomy & histology, metabolism)
• Mice
• Mice, SCID
• Obesity (etiology, metabolism, therapy)
• Organ Size
• Pancreas (cytology)
• Phenotype
• Stem Cell Transplantation
• Stem Cells (cytology)