title: The adult mouse and human pancreas contain rare multipotent stem cells that express insulin.
abstract: The search for putative precursor cells within the pancreas has been the focus of extensive research. Previously, we identified rare pancreas-derived multipotent precursor (PMP) cells in the mouse with the intriguing capacity to generate progeny in the pancreatic and neural lineages. Here, we establish the embryonic pancreas as the developmental source of PMPs through lineage-labeling experiments. We also show that PMPs express insulin and can contribute to multiple pancreatic and neural cell types in vivo. In addition, we have isolated PMPs from adult human islet tissue that are also capable of extensive proliferation, self-renewal, and generation of multiple differentiated pancreatic and neural cell types. Finally, both mouse and human PMP-derived cells ameliorated diabetes in transplanted mice. These findings demonstrate that the adult mammalian pancreas contains a population of insulin(+) multipotent stem cells and suggest that these cells may provide a promising line of investigation toward potential therapeutic benefit.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. simon.smukler@utoronto.ca
authors.forename: Simon R
authors.initials: SR
authors.lastname: Smukler
authors.forename: Margot E
authors.initials: ME
authors.lastname: Arntfield
authors.forename: Rozita
authors.initials: R
authors.lastname: Razavi
authors.forename: George
authors.initials: G
authors.lastname: Bikopoulos
authors.forename: Phillip
authors.initials: P
authors.lastname: Karpowicz
authors.forename: Raewyn
authors.initials: R
authors.lastname: Seaberg
authors.forename: Feihan
authors.initials: F
authors.lastname: Dai
authors.forename: Simon
authors.initials: S
authors.lastname: Lee
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ahrens
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wheeler
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000328:Adult; D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D010179:Pancreas / Q000166:cytology*; D010641:Phenotype
chemical_list: D007328:Insulin