title: Plasticity of human dedifferentiated adipocytes toward endothelial cells.
abstract: The process of cellular differentiation in terminally differentiated cells is thought to be irreversible, and these cells are thought to be incapable of differentiating into distinct cell lineages. Our previous study showed that mature adipocytes represent an alternative source of mesenchymal stem cells. Here, results showed the capacity of mature adipocytes to differentiate into endothelial-like cells, using the ability of these cells to revert into an immature phase without any relievable chromosomal alterations. Mature adipocytes were isolated from human omental and subcutaneous fat and were dedifferentiated in vitro. The resulting cells were subcultivated for endothelial differentiation and were analyzed for their expression of specific genes and proteins. Endothelial-like cells were harvested from the differentiation medium and were traditionally cultured to evaluate the endothelial markers and the karyotype. Cells cultured in specific medium formed tube-like structures and expressed several endothelial marker genes and proteins. The endothelial-like cells expressed significantly higher levels of vascular endothelium growth factor receptor 2, vascular endothelial cadherin, Von Willebrand factor, and CD133 than the untreated cells. These cells were positively stained for CD31 and vascular endothelial cadherin, markers of mature endothelial cells. Moreover, the low-density lipoprotein-uptake assay demonstrated a functionally endothelial differentiation of these cells. When these cells were harvested and reseeded in basal medium, they lost the endothelial markers and reacquired the typical mesenchymal stem cell markers and the ability to expand in a short time period. Moreover, karyotype analysis showed that these cells reverted into an immature phase without any karyotype alterations. In conclusion, the results showed that adipocytes exhibited a great plasticity toward the endothelial lineage, suggesting their possible use in cell therapy applications for vascular disease.
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy. Electronic address: a.poloni@univpm.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Poloni
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Maurizi
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Anastasi
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mondini
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Mattiucci
authors.affiliation: Laboratorio di Citogenetica e Genetica Molecolare, Clinica di Pediatria, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Discepoli
authors.affiliation: Laboratorio di Citogenetica e Genetica Molecolare, Clinica di Pediatria, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Tiberi
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mancini
authors.affiliation: Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Partelli
authors.affiliation: Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Maurizi
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Olivieri
authors.affiliation: Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
mesh_terms: D000071916:AC133 Antigen; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059785:Karyotype; D008077:Lipoproteins, LDL / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009852:Omentum / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D003470:Culture Media; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D014841:von Willebrand Factor; D000099152:Cadherin 5; C000606023:PROM1 protein, human; C000588866:KDR protein, human