TY - JOUR
T1 - Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas
AU - Hao, Ergeng
AU - Tyrberg, Björn
AU - Itkin-Ansari, Pamela
AU - Lakey, Jonathan R.T.
AU - Geron, Ifat
AU - Monosov, Edward Z.
AU - Barcova, Maria
AU - Mercola, Mark
AU - Levine, Fred
N1 - Funding Information:
We thank the islet isolation centers in Edmonton, Seattle, Minnesota and the Whittier Institute for providing human islets and nonendocrine cells, and C. Wright, O. Madsen, M. Magnuson and J. Hutton for providing antibodies and for discussions. We thank R. Bajpai for discussion and virus preparation. This work was funded by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation (to F.L., M.M. and J.R.T.L.), the Beta Cell Biology Consortium (to F.L.) and the Larry L. Hillblom Foundation (to B.T.).
PY - 2006/3
Y1 - 2006/3
N2 - The nature and even existence of adult pancreatic endocrine stem or progenitor cells is a subject of controversy in the field of beta-cell replacement for diabetes. One place to search for such cells is in the nonendocrine fraction of cells that remain after islet isolation, which consist of a mixture of epithelia and mesenchyme. Culture in G418 resulted in elimination of the mesenchymal cells, leaving a highly purified population of nonendocrine pancreatic epithelial cells (NEPECs). To evaluate their differentiation potential, NEPECs were heritably marked and transplanted under the kidney capsule of immunodeficient mice. When cotransplanted with fetal pancreatic cells, NEPECs were capable of endocrine differentiation. We found no evidence of beta-cell replication or cell fusion that could have explained the appearance of insulin positive cells from a source other than NEPECs. Nonendocrine-to-endocrine differentiation of NEPECs supports the existence of endocrine stem or progenitor cells within the epithelial compartment of the adult human pancreas.
AB - The nature and even existence of adult pancreatic endocrine stem or progenitor cells is a subject of controversy in the field of beta-cell replacement for diabetes. One place to search for such cells is in the nonendocrine fraction of cells that remain after islet isolation, which consist of a mixture of epithelia and mesenchyme. Culture in G418 resulted in elimination of the mesenchymal cells, leaving a highly purified population of nonendocrine pancreatic epithelial cells (NEPECs). To evaluate their differentiation potential, NEPECs were heritably marked and transplanted under the kidney capsule of immunodeficient mice. When cotransplanted with fetal pancreatic cells, NEPECs were capable of endocrine differentiation. We found no evidence of beta-cell replication or cell fusion that could have explained the appearance of insulin positive cells from a source other than NEPECs. Nonendocrine-to-endocrine differentiation of NEPECs supports the existence of endocrine stem or progenitor cells within the epithelial compartment of the adult human pancreas.
UR - http://www.scopus.com/inward/record.url?scp=33644828800&partnerID=8YFLogxK
U2 - 10.1038/nm1367
DO - 10.1038/nm1367
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C2 - 16491084
AN - SCOPUS:33644828800
SN - 1078-8956
VL - 12
SP - 310
EP - 316
JO - Nature Medicine
JF - Nature Medicine
IS - 3
ER -
