Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas.
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.
Huang
Haixia
H
Department of Cell Biology, Shanghai Second Medical University, Shanghai, China.
Tang
Xueming
X
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
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