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Research Paper|Volume 8, Issue 11|pp 2799—2813

Expansion induced microRNA changes in bone marrow mesenchymal stromal cells reveals interplay between immune regulation and cell cycle

Lotta Kilpinen1, Amarjit Parmar2,3, Dario Greco4, Matti Korhonen5, Petri Lehenkari6, Päivi Saavalainen2,3, Saara Laitinen1
  • 1Research and Development, Finnish Red Cross Blood Service, Helsinki, 00310, Finland
  • 2Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, 00014, Finland
  • 3Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, 00014, Finland
  • 4Institute of Biotechnology, University of Helsinki, Helsinki, 00014, Finland
  • 5Cell Therapy Services, Finnish Red Cross Blood Service, Helsinki, 00310, Finland
  • 6Department of Anatomy and Cell Biology, Translational and Cancer Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, 90014, Finland
Received: August 25, 2016Accepted: October 24, 2016Published: November 9, 2016
https://doi.org/10.18632/aging.101088

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.