Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells

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...

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Main Authors: Norlaily Mohd Ali, Lily Boo, Swee Keong Yeap, Huynh Ky, Dilan A. Satharasinghe, Woan Charn Liew, Han Kiat Ong, Soon Keng Cheong, Tunku Kamarul
Format: Article
Language:English
Published: PeerJ Inc. 2016-01-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/1536.pdf
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author Norlaily Mohd Ali
Lily Boo
Swee Keong Yeap
Huynh Ky
Dilan A. Satharasinghe
Woan Charn Liew
Han Kiat Ong
Soon Keng Cheong
Tunku Kamarul
author_facet Norlaily Mohd Ali
Lily Boo
Swee Keong Yeap
Huynh Ky
Dilan A. Satharasinghe
Woan Charn Liew
Han Kiat Ong
Soon Keng Cheong
Tunku Kamarul
author_sort Norlaily Mohd Ali
collection DOAJ
description 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).
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spelling doaj.art-a1243508bc314b26af3283ae846161812023-12-03T10:01:53ZengPeerJ Inc.PeerJ2167-83592016-01-014e153610.7717/peerj.1536Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cellsNorlaily Mohd Ali0Lily Boo1Swee Keong Yeap2Huynh Ky3Dilan A. Satharasinghe4Woan Charn Liew5Han Kiat Ong6Soon Keng Cheong7Tunku Kamarul8Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, MalaysiaFaculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, MalaysiaInstitute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaFaculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaInstitute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaInstitute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaFaculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, MalaysiaFaculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, MalaysiaTissue Engineering Group (TEG), National Orthopaedic Center of Excellence for Research and Learning (NOCERAL), Faculty of Medicine, Universiti Malaya, Kuala Lumpur, MalaysiaDecline 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).https://peerj.com/articles/1536.pdfHypoxiaDifferentiationAgeProliferationBone-marrowMesenchymal stem cells
spellingShingle Norlaily Mohd Ali
Lily Boo
Swee Keong Yeap
Huynh Ky
Dilan A. Satharasinghe
Woan Charn Liew
Han Kiat Ong
Soon Keng Cheong
Tunku Kamarul
Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells
PeerJ
Hypoxia
Differentiation
Age
Proliferation
Bone-marrow
Mesenchymal stem cells
title Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells
title_full Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells
title_fullStr Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells
title_full_unstemmed Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells
title_short Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells
title_sort probable impact of age and hypoxia on proliferation and microrna expression profile of bone marrow derived human mesenchymal stem cells
topic Hypoxia
Differentiation
Age
Proliferation
Bone-marrow
Mesenchymal stem cells
url https://peerj.com/articles/1536.pdf
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