title: Ontogeny of human umbilical cord perivascular cells: molecular and fate potential changes during gestation.
abstract: Human umbilical cord-derived perivascular cells (PVCs) are a recently characterized source of mesenchymal stromal cells that has gained much interest in the field of cellular therapeutics. However, very little is known about the changes in fate potential and restrictions that these cells undergo during gestational development. This study is the first to examine the phenotypic, molecular, and functional properties of first trimester (FTM)-derived PVCs, outlining properties that are unique to this population when compared to term (TERM) counterparts. FTM- and TERM-PVCs displayed analogous mesenchymal, perivascular, and immunological immunophenotypes. Both PVCs could be maintained in culture without alteration to these phenotypes or mesenchymal lineage differentiation potential. Some unique features of FTM-PVCs were uncovered in this study: (1) while the gene signatures of FTM- and TERM-PVCs were similar, key differences were observed, namely, that the Oct4A and Sox17 proteins were detected in FTM-PVCs, but not in TERM counterparts; (2) FTM-PVCs exhibited a greater proliferative potential; and (3) FTM-PVCs were more efficient in their in vitro differentiation toward selective mesenchymal cell types, including the chondrogenic and adipogenic lineages, as well as toward neuronal- and hepatocyte-like lineages, when compared to TERM-PVCs. Both PVCs were able to generate osteocytes and cardiomyocyte-like cells with similar efficiencies in vitro. Overall, FTM-PVCs show more plasticity than TERM-PVCs with regard to fate acquisition, suggesting that a restriction in multipotentiality is imposed on PVCs as gestation progresses. Taken together, our findings support the idea that PVCs from earlier in gestation may be better than later sources of multipotent stromal cells (MSCs) for some regenerative medicine applications.
authors.affiliation: CReATe Fertility Centre, Toronto, Ontario, Canada.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Leila
authors.initials: L
authors.lastname: Maghen
authors.forename: Shlomit
authors.initials: S
authors.lastname: Kenigsberg
authors.forename: Anouk-Martine
authors.initials: AM
authors.lastname: Teichert
authors.forename: Ashley W
authors.initials: AW
authors.lastname: Rammeloo
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shlush
authors.forename: Peter
authors.initials: P
authors.lastname: Szaraz
authors.forename: Schreiber
authors.initials: S
authors.lastname: Pereira
authors.forename: Ayub
authors.initials: A
authors.lastname: Lulat
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Shang-Mian
authors.initials: SM
authors.lastname: Yie
authors.forename: Andrée
authors.initials: A
authors.lastname: Gauthier-Fisher
authors.forename: Clifford L
authors.initials: CL
authors.lastname: Librach
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism; D020286:Pericytes / Q000166:cytology*; D055760:SOXF Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors