Reprogrammed Stomach Tissue as a Renewable Source of Functional β Cells for Blood Glucose Regulation

Cell Stem Cell. 2016 Mar 3;18(3):410-21. doi: 10.1016/j.stem.2016.01.003. Epub 2016 Feb 18.

Abstract

The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin(+) cells after undergoing cellular reprogramming. Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin(+) cells with close molecular and functional similarity to β cells. Induced GI insulin(+) cells can suppress hyperglycemia in a diabetic mouse model for at least 6 months and regenerate rapidly after ablation. Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control.

Publication types

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

MeSH terms

  • Animals
  • Cellular Reprogramming Techniques*
  • Cellular Reprogramming*
  • Gastric Mucosa / cytology
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / transplantation
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / transplantation
  • Mice