title: CD146 Expression Influences Periapical Cyst Mesenchymal Stem Cell Properties.
abstract: Recent studies have identified a new human dental derived progenitor cell population with multi-lineage differentiation potential referred to as human periapical cyst mesenchymal stem cells (hPCy-MSCs). In the present study, we compared two subpopulations of hPCy-MSCs characterised by the low or high expression of CD146 to establish whether this expression can regulate their stem cell properties. Using flow cytometry, we evaluated the stem cell marker profile of hPCy-MSCs during passaging. Furthermore, CD146Lowand CD146Highcells were sorted by magnetic beads and subsequently both cell populations were evaluated for differences in their proliferation, self-renewal, stem cell surface markers, stemness genes expression and osteogenic differentiation potential.We found that hPCy-MSCs possessed a stable expression of several mesenchymal stem cell surface markers, whereas CD146 expression declined during passaging.In addition, sorted CD146Lowcells proliferated significantly faster, displayed higher colony-forming unit-fibroblast capacity and showed higher expression of Klf4 when compared to the CD146Highsubset. Significantly, the osteogenic potential of hPCy-MSCs was greater in the CD146Lowthan in CD146Highpopulation. These results demonstrate that CD146 is spontaneously downregulated with passaging at both mRNA and protein levels and that the high expression of CD146 reduces the proliferative, self-renewal and osteogenic differentiation potential of hPCy-MSCs. In conclusion, our study demonstrates that changes in the expression of CD146 can influence the stem cell properties of hPCy-MSCs.
authors.affiliation: Tecnologica Research Institute, Biomedical Section, St. E. Fermi, Crotone, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Paduano
authors.affiliation: Calabrodental SRL, Experimental Medicine Section, Crotone, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Marrelli
authors.affiliation: Tecnologica Research Institute, Biomedical Section, St. E. Fermi, Crotone, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Palmieri
authors.affiliation: Tecnologica Research Institute, Biomedical Section, St. E. Fermi, Crotone, Italy. marco.tatullo@tecnologicasrl.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Tatullo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D051929:CD146 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D011842:Radicular Cyst / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051929:CD146 Antigen; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C497902:MCAM protein, human
keywords: CD146; Dental stem cells (DSCs); Human periapical cyst mesenchymal stem cells (hPCy-MSCs); MSC surface markers; Magnetic cell sorting; Osteogenic differentiation; Stemness genes