Nature Medicine
- 12, 310 - 316 (2006)
Published online: 19 February 2006; | doi:10.1038/nm1367
Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreasErgeng Hao1, 4, Björn Tyrberg1, 2, 4, Pamela Itkin-Ansari1, 2, Jonathan R T Lakey3, Ifat Geron1, Edward Z Monosov2, Maria Barcova2, Mark Mercola2 & Fred Levine1, 21
Rebecca and John Moores UCSD Cancer Center, University of California San Diego, 9500 Gilman Drive, MC 0816, La Jolla, California 92093, USA. 2
Stem Cells and Regeneration Program, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. 3
Clinical Islet Isolation Laboratory, University of Alberta, 1074 Dentistry/Pharmacy, Edmonton, Alberta, T6G 2N8, Canada. 4
These authors contributed equally to this work.
Correspondence should be addressed to Fred Levine flevine@ucsd.edu 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.
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