title: Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice.
abstract: Type 1 diabetes (T1D) is caused by autoimmune disease that leads to the destruction of pancreatic β-cells. Transplantation of cadaveric pancreatic organs or pancreatic islets can restore normal physiology. However, there is a chronic shortage of cadaveric organs, limiting the treatment of the majority of patients on the pancreas transplantation waiting list. Here, we hypothesized that human iPS cells can be directly differentiated into insulin producing cells (IPCs) capable of secreting insulin. Using a series of pancreatic growth factors, we successfully generated iPS cells derived IPCs. Furthermore, to investigate the capability of these cells to secrete insulin in vivo, the differentiated cells were transplanted under the kidney capsules of diabetic immunodeficient mice. Serum glucose levels gradually declined to either normal or near normal levels over 150 days, suggesting that the IPCs were secreting insulin. In addition, using MRI, a 3D organoid appeared as a white patch on the transplanted kidneys but not on the control kidneys. These organoids showed neo-vascularization and stained positive for insulin and glucagon. All together, these data show that a pancreatic organ can be created in vivo providing evidence that iPS cells might be a novel option for the treatment of T1D.
authors: Department of Internal Medicine, Division of Immunology, University of Iowa, Iowa City, IA, United States of America; Veterans Affairs Medical Center, Iowa City, IA, United States of America.
authors: Sudhanshu P
authors: SP
authors: Raikwar
authors: Department of Internal Medicine, Division of Immunology, University of Iowa, Iowa City, IA, United States of America; Veterans Affairs Medical Center, Iowa City, IA, United States of America.
authors: Eun-Mi
authors: EM
authors: Kim
authors: Division of Endocrinology & Metabolism, University of Iowa, Iowa City, IA, United States of America.
authors: William I
authors: WI
authors: Sivitz
authors: Central Microscopy Research facility, University of Iowa, Iowa City, IA, United States of America.
authors: Chantal
authors: C
authors: Allamargot
authors: Department of Radiology, University of Iowa, Iowa City, IA, United States of America.
authors: Daniel R
authors: DR
authors: Thedens
authors: Department of Internal Medicine, Division of Immunology, University of Iowa, Iowa City, IA, United States of America; Veterans Affairs Medical Center, Iowa City, IA, United States of America.
authors: Nicholas
authors: N
authors: Zavazava
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009940:Organoids; D010101:Oxygen Consumption; D033581:Stem Cell Transplantation
chemical_list: D001786:Blood Glucose
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