Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells.
Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.
Timper
Katharina
K
Department of Research, University Hospital, Basel, Switzerland.
Seboek
Dalma
D
Eberhardt
Michael
M
Linscheid
Philippe
P
Christ-Crain
Mirjam
M
Keller
Ulrich
U
Müller
Beat
B
Zulewski
Henryk
H
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005934:Glucagon / Q000096:biosynthesis*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D060850:LIM-Homeodomain Proteins; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D013004:Somatostatin / Q000096:biosynthesis*; D019089:Stem Cell Factor / Q000096:biosynthesis; D018800:Thy-1 Antigens / Q000096:biosynthesis; D014157:Transcription Factors
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018398:Homeodomain Proteins; D007328:Insulin; D007381:Intermediate Filament Proteins; D060850:LIM-Homeodomain Proteins; C577484:NES protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D019089:Stem Cell Factor; D018800:Thy-1 Antigens; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D013004:Somatostatin; D005934:Glucagon; D019009:Proto-Oncogene Proteins c-kit