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

Details

• Alternative Title:
  Cell Stem Cell
• Personal Author:
  Ariyachet, Chaiyaboot ; Tovaglieri, Alessio ; Xiang, Guanjue ; Lu, Jiaqi ; Shah, Manasvi S. ; Richmond, Camilla A. ; Verbeke, Catia ; Melton, Douglas A. ; Stanger, Ben Z. ; Mooney, David ; Shivdasani, Ramesh A. ; Mahony, Shaun ; Xia, Qing ; Breault, David T. ; Zhou, Qiao
• Description:
  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.
• Subjects:
  Animals Cellular Reprogramming Cellular Reprogramming Techniques Gastric Mucosa Insulin-Secreting Cells Mice
• Source:
  Cell Stem Cell. 18(3):410-421.
• Pubmed ID:
  26908146
• Pubmed Central ID:
  PMC4779391
• Document Type:
  Journal Article
• Funding:
  R01DK082889/DK/NIDDK NIH HHS/United States ; R01 DK084056/DK/NIDDK NIH HHS/United States ; U01 DK089536/DK/NIDDK NIH HHS/United States ; R01 DK106253/DK/NIDDK NIH HHS/United States ; P30 HD018655/HD/NICHD NIH HHS/United States ; P30DK034854/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; F32 DK107108/DK/NIDDK NIH HHS/United States ; R01 DK082889/DK/NIDDK NIH HHS/United States ; DP-0144-14-00/DP/NCCDPHP CDC HHS/United States ; P30HD18655/HD/NICHD NIH HHS/United States ; R01DK084056/DK/NIDDK NIH HHS/United States ; R00 DK077445/DK/NIDDK NIH HHS/United States
• Volume:
  18
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:62a973d61e0fa52d2d1e9056666eb24ad21bc473536fd33581f431ca265bcbbb
• Download URL:
  https://stacks.cdc.gov/view/cdc/40277/cdc_40277_DS1.pdf
• File Type:
  [PDF - 1.52 MB ]