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

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

Author information

1
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
2
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
3
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
4
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
5
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Division of Gastroenterology, Boston Children's Hospital, Boston, MA 02115, USA.
7
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
8
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
10
Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
11
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: qiao_zhou@harvard.edu.

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.

PMID:
26908146
PMCID:
PMC4779391
[Available on 2017-03-03]
DOI:
10.1016/j.stem.2016.01.003
[Indexed for MEDLINE]
Free PMC Article

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