title: 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: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Jennifer E
authors: JE
authors: Bruin
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Nelly
authors: N
authors: Saber
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Natalie
authors: N
authors: Braun
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Jessica K
authors: JK
authors: Fox
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Majid
authors: M
authors: Mojibian
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Ali
authors: A
authors: Asadi
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Campbell
authors: C
authors: Drohan
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors: Shannon
authors: S
authors: O'Dwyer
authors: BetaLogics Venture, Janssen R & D LLC, Raritan, NJ 08869, USA.
authors: Diana S
authors: DS
authors: Rosman-Balzer
authors: BetaLogics Venture, Janssen R & D LLC, Raritan, NJ 08869, USA.
authors: Victoria A
authors: VA
authors: Swiss
authors: BetaLogics Venture, Janssen R & D LLC, Raritan, NJ 08869, USA.
authors: Alireza
authors: A
authors: Rezania
authors: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: tim.kieffer@ubc.ca.
authors: Timothy J
authors: TJ
authors: Kieffer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D006943:Hyperglycemia; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D009929:Organ Size; D010179:Pancreas / Q000166:cytology*; D010641:Phenotype; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D007004:Hypoglycemic Agents; D005947:Glucose