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Mohd Ali N, Boo L, Yeap SK, Ky H, Satharasinghe DA, Liew WC, Ong HK, Cheong SK, Kamarul T. (2015) Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells. PeerJ PrePrints3:e1526v1https://doi.org/10.7287/peerj.preprints.1526v1
Decline in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSC) is often seen with older donors as compared to young. Although hypoxia is known as an approach to improve the therapeutic potential of MSC in term of cell proliferation and differentiation capacity, its effects on MSC from aged donors have not been well studied. To evaluate the influence of hypoxia on different age groups, MSC from young (<30 years) and aged (>60 years) donors were expanded under hypoxic (5% O2) and normal (20% O2) culture conditions. MSC from old donors exhibited a reduction in proliferation rate and differentiation potential together with the accumulation of senescence features compared to that of young donors. However, MSC cultured under hypoxic condition showed enhanced self-renewing and proliferation capacity in both age groups as compared to normal condition. Bioinformatic analysis of the gene ontology (GO) and KEGG pathway under hypoxic culture condition identified hypoxia-inducible miRNAs that were found to target transcriptional activity leading to enhanced cell proliferation, migration as well as decrease in growth arrest and apoptosis through the activation of multiple signaling pathways. Overall, differentially expressed miRNA provided additional information to describe the biological changes of young and aged MSCs expansion under hypoxic culture condition at the molecular level. Based on our findings, the therapeutic potential hierarchy of MSC according to donor’s age group and culture conditions can be categorized in the following order: young (hypoxia)> young (normoxia) > old aged (hypoxia) > old aged (normoxia).
This is a revised submission to PeerJ for review.
Supplementary data for figure 1A, 1B, 1E and 3.xlsx
Tables of raw data for Figure 1: MSCs characterization; A) Immunophenotyping of BM-MSC from young and aged donors (n=3). Representative graphs were all positive for CD105, CD90, CD44 and negative for CD19; B) Cumulative population doubling (CPD) of MSC expanded under normal and hypoxic conditions at p15; E) Representative reverse-transcription polymerase chain reaction run on 2% of agarose gel showing expression of aP2 and adiponectin by adipocytes and RUNX2 and osteopontin by osteocytes cells, induced from human bone-marrow mesenchymal stem cells. F) Senescence-associated β-Gal activity in MSC of normal vs Hypoxic at p15. Figure 4: Reproducibility of NGS and comparison of miRNA expression between NGS and qPCR analysis.
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