title: Effects of donor age, gender, and in vitro cellular aging on the phenotypic, functional, and molecular characteristics of mouse bone marrow-derived mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are a very important adult stem cell population with a multitude of potential applications in regenerative medicine. The thorough characterization of the bone marrow MSC (BM-MSC) population derived from the BALB/c species was essential, considering the significance of the murine model amongst animal models. In the present study, we examined the effect of gender, age, and in vitro culture on the basic properties (proliferation, differentiation, and immunosuppressive potential) of BM-MSCs. We found a decline in the progenitor frequencies from the BM of adult mice, lower MSC frequencies in all female donors, and an increase in the BM-MSC proliferation rate upon in vitro propagation. We also examined BM-MSCs for the expression of the 3 major embryonic stem cell transcription factors, Oct3/4, Sox-2, and Nanog, as well as 2 mRNA binding proteins, coding region determinant binding protein/insulin-like growth factor 2 mRNA binding protein 1 (Crd-bp/Imp1) and Deleted in azoospermia-like (Dazl), which are expressed in primitive stem cells, umbilical cord blood-hematopoietic stem cells and amniotic fluid stem cells, respectively. Further, it has been reported that these 2 genes are critical for embryonic development. In this study, therefore, we report, for the first time, the expression of Crd-bp/Imp1 and Dazl in BM-MSCs. Dazl, Oct3/4, and Sox2 were detected in relatively low levels in contrast to Crd-bp/Imp1, its major target c-Myc, as well as Nanog, which were expressed redundantly, irrespective of sex, donor age, or in vitro passaging. These findings could further support the extrinsic theory of aging of the MSC population and the potential implication of embryonic genes in adult stem cell physiology.
authors.affiliation: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Katsara
authors.forename: Louisa G
authors.initials: LG
authors.lastname: Mahaira
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Iliopoulou
authors.forename: Ardiana
authors.initials: A
authors.lastname: Moustaki
authors.forename: Aristidis
authors.initials: A
authors.lastname: Antsaklis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Loutradis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stefanidis
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Baxevanis
authors.forename: Michael
authors.initials: M
authors.lastname: Papamichail
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Perez
mesh_terms: D000367:Age Factors; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D016922:Cellular Senescence; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C519161:CRD-BP protein, mouse; C508515:DAZL protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016601:RNA-Binding Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse