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

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1536 ◽  
Author(s):  
Norlaily Mohd Ali ◽  
Lily Boo ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
Dilan A. Satharasinghe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Culture Condition ◽  
Therapeutic Potential ◽  
Age Groups ◽  
Human Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Differentiation Potential

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).

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

2015 ◽  
Author(s):  
Norlaily Mohd Ali ◽  
Lily Boo ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
Dilan A Satharasinghe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Culture Condition ◽  
Therapeutic Potential ◽  
Age Groups ◽  
Human Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Differentiation Potential

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).

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

2015 ◽  
Author(s):  
Norlaily Mohd Ali ◽  
Lily Boo ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
Dilan A Satharasinghe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Culture Condition ◽  
Therapeutic Potential ◽  
Age Groups ◽  
Human Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Differentiation Potential

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).

Purinergic Stimulation of Human Bone Marrow-Derived Mesenchymal Stem Cells Modulate Their Function and Differentiation Potential.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3848-3848
Author(s):  
Marilena Ciciarello ◽  
Valentina Salvestrini ◽  
Davide Ferrari ◽  
Sara Gulinelli ◽  
Roberta Zini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Human Bone ◽  
Differentiation Potential ◽  
Qrt Pcr ◽  
Differentiated Cells

Abstract Abstract 3848 Introduction: Human bone marrow derived Mesenchymal Stem Cells (hMSCs) are adult multipotent cells. hMSCs differentiate in vitro and in vivo into several tissue lineages originating from the three germinal layers making them attractive candidates for bioengineering and cellular therapy. Thus, it seems of great relevance to search putative messengers and signalling able to modulate their proliferation and differentiation. Nucleotides triphosphates are extracellular messengers binding to specific receptors (P2Rs) that modulate cell functions depending on the cell type. Controversial information is available on P2 expression and activity in hMSCs. Methods and Results: Here we found that hMSCs expressed several P2R subtypes. hMSCs were very resistant to the cytotoxic effects of high concentrations of ATP, as demonstrated by the lack of morphological and mitochondrial changes or release of intracellular markers of cell death. Gene expression profiling revealed that ATP treatment down-regulated cell proliferation and up-regulated cell migration genes in hMSCs. Functional studies confirmed the inhibitory activity of ATP on proliferation and clonogenic ability of hMSCs. Furthermore, ATP potentiated the chemotactic response of hMSCs to the chemokine CXCL12, and increased their spontaneous migration. In vivo, xenotransplant experiments showed that the homing capacity of hMSCs to murine bone marrow was increased by ATP pre-treatment. Moreover, ATP increased pro-inflammatory cytokines production (IL-2, IFN-g, IL-12p70), while decreased secretion of the anti-inflammatory cytokine IL-10. This finding was associated with the reduced ability of ATP-treated hMSC of inhibiting T-cell proliferation. Microarrays data suggested that several genes implicated in hMSC differentiation can be modulated by ATP treatment. To further investigate this issue, hMSCs cells were cultured under adipogenic or osteogenic conditions and were transiently exposed to ATP before starting differentiation or continuously exposed to ATP for the first 3 days of differentiation induction. We demonstrated that adipogenesis-related accumulation of lipids, analyzed by Oil red O staining, was more evident in ATP treated cultures. Furthermore, quantitative real time PCR (qRT-PCR) assay showed that mRNA expression of PPARg, a transcription factor early up-regulated during adipogenesis, was significantly increased in hMSCs differentiated cells treated with ATP. In osteogenic condition, analysis of mineralized area through Alizarin Red staining, indicated that ATP treatment enhanced the extent of mineralization compared to untreated control. The expression of RUNX2, a key transcription factor in osteogenesis, analyzed by qRT-PCR in differentiated cells confirmed data obtained in Alizarin-based assay. Conclusions: These data demonstrated that purinergic signalling modulates biological functions and differentiation potential of hMSCs. Disclosures: No relevant conflicts of interest to declare.

The Centromeric Protein, CEN(P)-F, a Marker of Cell Proliferation Is Regulated by Hypoxia in Human Mesenchymal Stem Cells and Their Bone Marrow Stromal Progeny.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1385-1385
Author(s):  
Suzanne M. Watt ◽  
Sarah Hale ◽  
Dilair Baban ◽  
Maria Roubelakis ◽  
Meis Moukayed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cell Division ◽  
Stromal Cells ◽  
Significant Proportion ◽  
Human Mesenchymal Stem Cells ◽  
Cell Number ◽  
Centromeric Protein

Abstract Human bone marrow mesenchymal stem cells (MSC) are multipotent progenitors that generate osteoblasts, chondrocytes, adipocytes, myoblasts and the bone marrow stromal cells that support hematopoiesis. Although the bone marrow microenvironment is hypoxic, little is known about the maintenance and response of MSC and their bone marrow stromal progeny to hypoxia. Using cDNA microarray hybridization technologies, we show, for the first time, that a total of 231 mRNAs in cultured MSCs are regulated by short exposures (4–48hrs) to hypoxia. These include known hypoxia-responsive genes, such as BHLHB2, PGK1, GLUT-1 and VEGF. Interestingly, we demonstrate that a significant proportion of genes involved in cell growth, proliferation or survival are also regulated by hypoxia in these cells. Amongst these, we have identified the centromeric protein CENP-F as a novel gene up-regulated in cultured MSCs by hypoxia. This up-regulation results in an increased level of CENP-F protein. The hypoxic stimulus also enhances cell division in the bone marrow MSC-derived stromal cells, resulting in a doubling in cell number within 24hrs. This contrasts with the effects of hypoxia on mature endothelial cells (EC), where recruitment into cell cycle is unchanged. Our demonstration that hypoxia promotes cell division and cell proliferation in the bone marrow stromal progeny of human MSC may have wider implications for the regulated growth and survival of other stem cells in hypoxic microenvironmental niches.

Sign in / Sign up

Export Citation Format

Share Document