title: Expansion induced microRNA changes in bone marrow mesenchymal stromal cells reveals interplay between immune regulation and cell cycle.
abstract: Mesenchymal stromal cells (MSC) are currently used in many cell based therapies. Prior to use in therapy, extensive expansion is required. We used microarray profiling to investigate expansion induced miRNA and mRNA expression changes of bone marrow MSCs (BM-MSCs) derived from old and young donors. The expression levels of 36 miRNAs were altered in cells derived from the old and respectively 39 miRNAs were altered in cells derived from young donors. Of these, only 12 were differentially expressed in both young and old donor BM-MSCs, and their predicted target mRNAs, were mainly linked to cell proliferation and senescence. Further qPCR verification showed that the expression of miR-1915-3p, miR-1207, miR-3665, and miR-762 correlated with the expansion time at passage 8. Previously described BM-MSC-specific miRNA fingerprints were also detected but these remained unchanged during expansion. Interestingly, members of well-studied miR-17/92 cluster, involved in cell cycle regulation, aging and also development of immune system, were down-regulated specifically in cells from old donors. The role of this cluster in MSC functionality is worth future studies since it links expansion, aging and immune system together.
authors.affiliation: Research and Development, Finnish Red Cross Blood Service, Helsinki, 00310, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Kilpinen
authors.affiliation: Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, 00014, Finland.|Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, 00014, Finland.
authors.forename: Amarjit
authors.initials: A
authors.lastname: Parmar
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, 00014, Finland.
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.affiliation: Cell Therapy Services, Finnish Red Cross Blood Service, Helsinki, 00310, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Korhonen
authors.affiliation: Department of Anatomy and Cell Biology, Translational and Cancer Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, 90014, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
authors.affiliation: Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, 00014, Finland.|Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, 00014, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Saavalainen
authors.affiliation: Research and Development, Finnish Red Cross Blood Service, Helsinki, 00310, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Laitinen
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation / Q000235:genetics*; D016922:Cellular Senescence; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: SOCS3; mesenchymal stromal cells; microRNA; senescence