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

Chaiyaboot Ariyachet, Alessio Tovaglieri, Guanjue Xiang, Jiaqi Lu, Manasvi S. Shah, Camilla A. Richmond, Catia Verbeke, Douglas A. Melton, Ben Z. Stanger, David Mooney, Ramesh A. Shivdasani, Shaun Mahony, Qing Xia, David T. Breault, Qiao Zhou

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Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)410-421
Number of pages12
JournalCell Stem Cell
Volume18
Issue number3
DOIs
StatePublished - Mar 3 2016

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Ariyachet, C., Tovaglieri, A., Xiang, G., Lu, J., Shah, M. S., Richmond, C. A., Verbeke, C., Melton, D. A., Stanger, B. Z., Mooney, D., Shivdasani, R. A., Mahony, S., Xia, Q., Breault, D. T., & Zhou, Q. (2016). Reprogrammed Stomach Tissue as a Renewable Source of Functional β Cells for Blood Glucose Regulation. Cell Stem Cell, 18(3), 410-421. https://doi.org/10.1016/j.stem.2016.01.003