Human iPS Cell-Derived Insulin Producing Cells Form Vascularized Organoids under the Kidney Capsules of Diabetic Mice

PLoS One

Nicholas Zavazava¹  Sudhanshu P. Raikwar²  William I. Sivitz²  Daniel R. Thedens³  Eun-Mi Kim⁴  Chantal Allamargot⁴ 

[1] Central Microscopy Research facility, University of Iowa, Iowa City, IA, United States of America;Department of Internal Medicine, Division of Immunology, University of Iowa, Iowa City, IA, United States of America;Division of Endocrinology & Metabolism, University of Iowa, Iowa City, IA, United States of America;Veterans Affairs Medical Center, Iowa City, IA, United States of America

关键词: Insulin;    Cell differentiation;    Induced pluripotent stem cells;    Renal transplantation;    Diabetes mellitus;    Kidneys;    Organoids;    Blood sugar;   

DOI  :  10.1371/journal.pone.0116582

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY