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

• Published in: Stem cell reports Vol. 4; no. 4; pp. 605 - 620
• Main Authors: Bruin, Jennifer E, Saber, Nelly, Braun, Natalie, Fox, Jessica K, Mojibian, Majid, Asadi, Ali, Drohan, Campbell, O'Dwyer, Shannon, Rosman-Balzer, Diana S, Swiss, Victoria A, Rezania, Alireza, Kieffer, Timothy J
• Format: Journal Article
• Language: English
• Published: United States Elsevier 14.04.2015
• Subjects: Animals; Cell Differentiation; Cell- and Tissue-Based Therapy; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - 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; Insulin-Secreting Cells - metabolism; Islets of Langerhans - cytology; Liver - anatomy & histology; Liver - metabolism; Mice; Mice, SCID; Obesity - etiology; Obesity - metabolism; Obesity - therapy; Organ Size; Pancreas - cytology; Phenotype; Stem Cell Transplantation; Stem Cells - cytology
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2015.02.011

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.