title: Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells.
abstract: 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).
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman , Cheras, Selangor , Malaysia.
authors.forename: Norlaily
authors.initials: N
authors.lastname: Mohd Ali
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman , Cheras, Selangor , Malaysia.
authors.forename: Lily
authors.initials: L
authors.lastname: Boo
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia , Serdang, Selangor , Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, Cantho, Vietnam.
authors.forename: Huynh
authors.initials: H
authors.lastname: Ky
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka.
authors.forename: Dilan A
authors.initials: DA
authors.lastname: Satharasinghe
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia , Serdang, Selangor , Malaysia.
authors.forename: Woan Charn
authors.initials: WC
authors.lastname: Liew
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman , Cheras, Selangor , Malaysia.
authors.forename: Han Kiat
authors.initials: HK
authors.lastname: Ong
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia; Cryocord Sdn Bhd, Cyberjaya, Malaysia.
authors.forename: Soon Keng
authors.initials: SK
authors.lastname: Cheong
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Center of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya , Kuala Lumpur , Malaysia.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
keywords: Age; Bone-marrow; Differentiation; Hypoxia; Mesenchymal stem cells; MicroRNA; Next generation sequencing; Proliferation