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
- 1 Research and Development, Finnish Red Cross Blood Service, Helsinki, 00310, Finland
- 2 Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, 00014, Finland
- 3 Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, 00014, Finland
- 4 Institute of Biotechnology, University of Helsinki, Helsinki, 00014, Finland
- 5 Cell Therapy Services, Finnish Red Cross Blood Service, Helsinki, 00310, Finland
- 6 Department 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, 2016 Accepted: October 24, 2016 Published: November 9, 2016
https://doi.org/10.18632/aging.101088How to Cite
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.