Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets.
Mesenchymal cells in the developing pancreas express the neural stem cell marker nestin and the transcription factor islet-1 (Isl-1). Using defined culture conditions we isolated on a single cell basis nestin producing cells from human pancreatic islets. These cells were immortalized with lentiviral vectors coding for telomerase and mBmi. They are positive for Isl-1 and nestin and have the potential to adopt a pancreatic endocrine phenotype with expression of critical transcription factors including Ipf-1, Isl-1, Ngn-3, Pax4, Pax6, Nkx2.2, and Nkx6.1 as well as the islet hormones insulin, glucagon, and somatostatin. In addition, they can be differentiated into human albumin producing cells in vivo when grafted into a SCID mouse liver. In accordance with a mesenchymal phenotype, the cells were also able to adopt adipocytic or osteocytic phenotypes in vitro. In conclusion, cultured pancreatic islets contain nestin and Isl-1 positive mesenchymal stem cells with multipotential developmental capacity.
Eberhardt
Michael
M
Division for Endocrinology, Diabetes and Clinical Nutrition, Department of Research, University Hospital Basel, Switzerland.
Salmon
Patrick
P
von Mach
Marc-Alexander
MA
Hengstler
Jan Georg
JG
Brulport
Marc
M
Linscheid
Philippe
P
Seboek
Dalma
D
Oberholzer
José
J
Barbero
Andrea
A
Martin
Ivan
I
Müller
Beat
B
Trono
Didier
D
Zulewski
Henryk
H
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D016086:Lentivirus / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D064231:Nestin; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D010006:Osteoblasts / Q000378:metabolism; D014157:Transcription Factors
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000418:Albumins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D060850:LIM-Homeodomain Proteins; C577484:NES protein, human; C000715631:NKX2-2 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C000715627:Nkx2-2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1