Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro

Autor: Mélanie Marchand, Florence de Fraipont, Marie-Jeanne Richard, Pierre Savatier, Pierre‐Yves Benhamou, Marie Favrot, Domenico Bosco, C. Moriscot
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Homeodomain Proteins/biosynthesis/genetics/metabolism
Biological Markers/metabolism
Cellular differentiation
RNA
Messenger/metabolism
Adipocytes/cytology/metabolism
Mice
Insulin-Secreting Cells
Adipocytes
Insulin
Insulin/biosynthesis/genetics
Cells
Cultured
Stem cell transplantation for articular cartilage repair
Bone Marrow Cells/cytology/metabolism
ddc:617
Reverse Transcriptase Polymerase Chain Reaction
Cell Differentiation
Telomere
Cell biology
medicine.anatomical_structure
Mesenchymal Stromal Cells/cytology/metabolism
Hepatocyte Nuclear Factor 3-beta
Insulin-Secreting Cells/cytology/metabolism
Molecular Medicine
Stem cell
endocrine system
Hepatocyte Nuclear Factor 3-beta/biosynthesis/genetics
Clinical uses of mesenchymal stem cells
Bone Marrow Cells
Biology
Adenoviridae
medicine
Animals
Humans
RNA
Messenger
Adenoviridae/genetics
Telomere/metabolism
Homeodomain Proteins
Trans-Activators/biosynthesis/genetics
Multipotent Stem Cells
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Transcription Factors/biosynthesis/genetics
Coculture Techniques
Multipotent Stem Cell
Immunology
Trans-Activators
Ectopic expression
Bone marrow
Multipotent Stem Cells/cytology/metabolism
Biomarkers
Developmental Biology
Transcription Factors
Zdroj: Stem Cells, Vol. 23, No 4 (2005) pp. 594-603
ISSN: 1066-5099
Popis: Multipotential stem cells can be selected from the bone marrow by plastic adhesion, expanded, and cultured. They are able to differentiate not only into multiple cell types, including cartilage, bone, adipose and fibrous tissues, and myelosupportive stroma, but also into mesodermal (endothelium), neuroectodermal, or endodermal (hepatocytes) lineages. Our goal was to characterize the multipotential capacities of human mesenchymal stem cells (hMSCs) and to evaluate their ability to differentiate into insulin-secreting cells in vitro. hMSCs were obtained from healthy donors, selected by plastic adhesion, and phenotyped by fluorescence-activated cell sorter and reverse transcription-polymerase chain reaction analysis before and after infection with adenoviruses coding for mouse IPF1, HLXB9, and FOXA2 transcription factors involved early in the endocrine developmental pathway. We found that native hMSCs have a pluripotent phenotype (OCT4 expression and high telomere length) and constitutively express NKX6-1 at a low level but lack all other transcription factors implicated in beta-cell differentiation. In all hMSCs, we detected mRNA of cytokeratin 18 and 19, epithelial markers present in pancreatic ductal cells, whereas proconvertase 1/3 mRNA expression was detected only in some hMSCs. Ectopic expression of IPF1, HLXB9, and FOXA2 with or without islet coculture or islet-conditioned medium results in insulin gene expression. In conclusion, our results demonstrated that in vitro human bone marrow stem cells are able to differentiate into insulin-expressing cells by a mechanism involving several transcription factors of the beta-cell developmental pathway when cultured in an appropriate microenvironment.
Databáze: OpenAIRE
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