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.

Bone marrow-derived humoral factors suppress oxidative phosphorylation, upregulate TSG-6, and improve therapeutic effects on liver injury of mesenchymal stem cells

“…Seven of these miRNAs targeted numerous genes related to the change of OXPHOS activity observed in the mRNA microarray of BM-MSCs cultured in 20-nm-filtered BMC-CM vs BMC-CM, which were selected in accordance with the "microRNA Target Filter" function of IPA (Table 3). (19,20) Agonists, and the associated negative controls (mirVana TM ; Life Technologies, Carlsbad, CA) for each of the selected seven miRNAs were purchased and Table 2. Increasing miRNA expression in the BMC CM incubation process Under bar: miRNAs selected for the transduction experiment on BM MSC.…”

Concise Review: TLR Pathway-miRNA Interplay in Mesenchymal Stromal Cells: Regulatory Roles and Therapeutic Directions

“…The association between miRNAs and cellular senescence (either as a result of donor age or culture expansion) is also supported by similar evidence from other studies. In a study with human BM‐MSCs, members of the miR‐17/92 cluster involved in the development of the immune system were downregulated during culture and was more pronounced in cells from old donors . In another study, miRNAs were shown to not only be differentially expressed by MSCs from different sources (UC and cord blood) but also differed in their role in the senescence process .…”

miR-4651 inhibits cell proliferation of gingival mesenchymal stem cells by inhibiting HMGA2 under nifedipine treatment

“…18,19 Recently, increasing numbers of studies have indicated that miRNAs regulate biological processes such as cell proliferation, apoptosis, the cell cycle and cell differentiation. [20][21][22][23][24] In addition, miRNAs play an important role in the occurrence, development and prognosis of human cancer. 25 Previously, our miRNA array analysis results showed that some miRNAs, such as miR-3940-5p and miR-4651, were differentially expressed in gingiva from patients treated with NIF.…”