title: Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow.
abstract: Human bone marrow mesenchymal stem cells (hBM-MSCs) hold promise for treating incurable diseases and repairing of damaged tissues. However, hBM-MSCs face the disadvantages of painful invasive isolation and limited cell numbers. In this study we assessed characteristics of MSCs isolated from residual human bone marrow transplantation material and expanded to clinically relevant numbers at passages 3-4 and 6-7. Results indicated that early passage hBM-MSCs are genomically stable and retain identity and high proliferation capacity. Despite the chromosomal stability, the cells became senescent at late passages, paralleling the slower proliferation, altered morphology and immunophenotype. By qRT-PCR array profiling, we revealed 13 genes and 33 miRNAs significantly differentially expressed in late passage cells, among which 8 genes and 30 miRNAs emerged as potential novel biomarkers of hBM-MSC aging. Functional analysis of genes with altered expression showed strong association with biological processes causing cellular senescence. Altogether, this study revives hBM as convenient source for cellular therapy. Potential novel markers provide new details for better understanding the hBM-MSC senescence mechanisms, contributing to basic science, facilitating the development of cellular therapy quality control, and providing new clues for human disease processes since senescence phenotype of the hematological patient hBM-MSCs only very recently has been revealed.
authors.affiliation: Department of Botany and Genetics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.|Biobank, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Gabrielis
authors.initials: G
authors.lastname: Kundrotas
authors.affiliation: Department of Botany and Genetics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors.forename: Evelina
authors.initials: E
authors.lastname: Gasperskaja
authors.affiliation: Department of Botany and Genetics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors.forename: Grazina
authors.initials: G
authors.lastname: Slapsyte
authors.affiliation: Biobank, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Zivile
authors.initials: Z
authors.lastname: Gudleviciene
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasko
authors.affiliation: Biobank, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Ausra
authors.initials: A
authors.lastname: Stumbryte
authors.affiliation: Biobank, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Regina
authors.initials: R
authors.lastname: Liudkeviciene
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D042822:Genomic Instability; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
keywords: Gerotarget; PCR arrays; genomic stability; human mesenchymal stem cells; long-term expansion; senescence markers