Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells

Cell Rep. 2020 Jul 14;32(2):107894. doi: 10.1016/j.celrep.2020.107894.


Understanding the root causes of autoimmune diseases is hampered by the inability to access relevant human tissues and identify the time of disease onset. To examine the interaction of immune cells and their cellular targets in type 1 diabetes, we differentiated human induced pluripotent stem cells into pancreatic endocrine cells, including β cells. Here, we describe an in vitro platform that models features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells. We demonstrate a cell-type-specific response by autologous immune cells against induced pluripotent stem cell-derived β cells, along with a reduced effect on α cells. This approach represents a path to developing disease models that use patient-derived cells to predict the outcome of an autoimmune response.

Keywords: disease modeling; endoplasmic reticulum stress; induced pluripotent stem cell-derived β cells; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Endoplasmic Reticulum Stress
  • Glucagon-Secreting Cells / pathology
  • Humans
  • Insulin-Secreting Cells / pathology
  • Lymphocyte Activation / immunology
  • Mice
  • Models, Biological*
  • Pluripotent Stem Cells / pathology*
  • T-Lymphocytes / immunology