title: Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas.
abstract: Demand for donations to meet the requirements of pancreas or islet transplantation has prompted the search for alternative sources of beta-cell replacement therapy. Earlier studies identified nestin-positive islet-derived progenitor cells (NIPs) residing in human pancreas. In the present study, we isolated and cultured human fetal NIPs that express stem cell marker ABCG2/BCRP1. In confluent cultures, NIPs formed three-dimensional islet-like cell clusters (ICCs). During differentiation, NIP-derived ICCs showed numerous pancreatic lineage transcripts including insulin, whereas ABCG2 and nestin expression fell concomitantly. In addition, ICCs displayed the ability to reverse hyperglycemia in diabetic NOD-SCID mice, as well as infiltrate and form well-differentiated structures in normal mice. These cells can be cloned repeatedly and maintained in long-term culture. Our studies are the first to show NIPs derived from human fetal pancreas, which may have significant implications for future applications in stem cell therapy of diabetes.
authors.affiliation: Department of Cell Biology, Shanghai Second Medical University, Shanghai, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Huang
authors.forename: Xueming
authors.initials: X
authors.lastname: Tang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D010179:Pancreas / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D012333:RNA, Messenger