Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential
Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological “niches” for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one devel...
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| Veröffentlicht in: | Cell and tissue research 2010-07, Vol.341 (1), p.111-120 |
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| creator | Valorani, M. G Germani, A Otto, W. R Harper, L Biddle, A Khoo, C. P Lin, W. R Hawa, M. I Tropel, P Patrizi, M. P Pozzilli, P Alison, M. R |
| description | Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological “niches” for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1⁺ as well as Sca-1⁺/CD44⁺double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor γ (Pparγ), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation. |
| doi_str_mv | 10.1007/s00441-010-0982-8 |
| format | Article |
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G ; Germani, A ; Otto, W. R ; Harper, L ; Biddle, A ; Khoo, C. P ; Lin, W. R ; Hawa, M. I ; Tropel, P ; Patrizi, M. P ; Pozzilli, P ; Alison, M. R</creator><creatorcontrib>Valorani, M. G ; Germani, A ; Otto, W. R ; Harper, L ; Biddle, A ; Khoo, C. P ; Lin, W. R ; Hawa, M. I ; Tropel, P ; Patrizi, M. P ; Pozzilli, P ; Alison, M. R</creatorcontrib><description>Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological “niches” for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1⁺ as well as Sca-1⁺/CD44⁺double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor γ (Pparγ), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation.</description><identifier>ISSN: 0302-766X</identifier><identifier>EISSN: 1432-0878</identifier><identifier>DOI: 10.1007/s00441-010-0982-8</identifier><identifier>PMID: 20496083</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Adipogenesis ; adipose tissue ; Adipose Tissue - cytology ; Adipose tissues ; Animals ; Ataxin-1 ; Ataxins ; Biomarkers - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Body fat ; CD44 ; Cell culture (Mouse) ; Cell Cycle ; Cell Hypoxia ; Cell Proliferation ; Cell Survival ; Cells ; Cells, Cultured ; Cellular biology ; Differentiation ; Gene expression ; Human Genetics ; Hyaluronan Receptors - metabolism ; Hypoxia ; Lipoprotein lipase ; Male ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Mice ; mMSCs ; Molecular Medicine ; Nerve Tissue Proteins - metabolism ; Nuclear Proteins - metabolism ; Protein binding ; Proteomics ; Regular Article ; Rodents ; Sca-1 ; Stem cells</subject><ispartof>Cell and tissue research, 2010-07, Vol.341 (1), p.111-120</ispartof><rights>Springer-Verlag 2010</rights><rights>COPYRIGHT 2010 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-81c8d44569f66a7a0d1d21f729df24e05306eb54b0c7208abcaac9fba2b176963</citedby><cites>FETCH-LOGICAL-c524t-81c8d44569f66a7a0d1d21f729df24e05306eb54b0c7208abcaac9fba2b176963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00441-010-0982-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00441-010-0982-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27911,27912,41475,42544,51306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20496083$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valorani, M. G</creatorcontrib><creatorcontrib>Germani, A</creatorcontrib><creatorcontrib>Otto, W. R</creatorcontrib><creatorcontrib>Harper, L</creatorcontrib><creatorcontrib>Biddle, A</creatorcontrib><creatorcontrib>Khoo, C. P</creatorcontrib><creatorcontrib>Lin, W. R</creatorcontrib><creatorcontrib>Hawa, M. I</creatorcontrib><creatorcontrib>Tropel, P</creatorcontrib><creatorcontrib>Patrizi, M. P</creatorcontrib><creatorcontrib>Pozzilli, P</creatorcontrib><creatorcontrib>Alison, M. R</creatorcontrib><title>Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential</title><title>Cell and tissue research</title><addtitle>Cell Tissue Res</addtitle><addtitle>Cell Tissue Res</addtitle><description>Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological “niches” for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1⁺ as well as Sca-1⁺/CD44⁺double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor γ (Pparγ), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation.</description><subject>Adipogenesis</subject><subject>adipose tissue</subject><subject>Adipose Tissue - cytology</subject><subject>Adipose tissues</subject><subject>Animals</subject><subject>Ataxin-1</subject><subject>Ataxins</subject><subject>Biomarkers - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Body fat</subject><subject>CD44</subject><subject>Cell culture (Mouse)</subject><subject>Cell Cycle</subject><subject>Cell Hypoxia</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Differentiation</subject><subject>Gene expression</subject><subject>Human Genetics</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Hypoxia</subject><subject>Lipoprotein lipase</subject><subject>Male</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Mice</subject><subject>mMSCs</subject><subject>Molecular Medicine</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Protein binding</subject><subject>Proteomics</subject><subject>Regular Article</subject><subject>Rodents</subject><subject>Sca-1</subject><subject>Stem cells</subject><issn>0302-766X</issn><issn>1432-0878</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkktv1DAUhSMEokPhB7CBCCRYpb1-xHGW1fAoUiUWpRI7y3FuZlwldrATqbPmj-OQ8ihCIC8s29858rk6WfaUwAkBqE4jAOekAAIF1JIW8l62IZzRAmQl72cbYECLSojPR9mjGK8BCBeifpgdUeC1AMk22dfzw-hvrM6tMwF1xJhfGl2Q0-0bznPjC7wZA8ZovUtIPszBOswHjOjM_jDoPo8TDrnBvo-5dm2Obq-dSTbTHm3IdWtHv0NnTd7arsOAbrJ6WuxGP30_9I-zB53uIz653Y-zq3dvP23Pi4uP7z9szy4KU1I-FZIY2XJeiroTQlcaWtJS0lW0bjvKEUoGApuSN2AqClI3RmtTd42mDalELdhx9nr1HYP_MmOc1GDj8nPt0M9RVSWXFVBB_k8yJhhUEhL54g_y2s_BpRhKgKiBCF4m6OUK7XSPyrrOT0GbxVKdsZLXjJWMJ-rkL1RaLQ7WeIedTfd3BK9-E-xR99M--n5ephvvgmQFTfAxBuzUGOygw0ERUEuT1NoklZqkliYpmTTPboPNzYDtT8WP6iSArkBMT26H4Vfyf7k-X0Wd9krvgo3q6pICYUCkKNPs2Tc-p9rr</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Valorani, M. 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G</au><au>Germani, A</au><au>Otto, W. R</au><au>Harper, L</au><au>Biddle, A</au><au>Khoo, C. P</au><au>Lin, W. R</au><au>Hawa, M. I</au><au>Tropel, P</au><au>Patrizi, M. P</au><au>Pozzilli, P</au><au>Alison, M. R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential</atitle><jtitle>Cell and tissue research</jtitle><stitle>Cell Tissue Res</stitle><addtitle>Cell Tissue Res</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>341</volume><issue>1</issue><spage>111</spage><epage>120</epage><pages>111-120</pages><issn>0302-766X</issn><eissn>1432-0878</eissn><abstract>Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological “niches” for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1⁺ as well as Sca-1⁺/CD44⁺double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor γ (Pparγ), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>20496083</pmid><doi>10.1007/s00441-010-0982-8</doi><tpages>10</tpages></addata></record> |
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| ispartof | Cell and tissue research, 2010-07, Vol.341 (1), p.111-120 |
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| subjects | Adipogenesis adipose tissue Adipose Tissue - cytology Adipose tissues Animals Ataxin-1 Ataxins Biomarkers - metabolism Biomedical and Life Sciences Biomedicine Body fat CD44 Cell culture (Mouse) Cell Cycle Cell Hypoxia Cell Proliferation Cell Survival Cells Cells, Cultured Cellular biology Differentiation Gene expression Human Genetics Hyaluronan Receptors - metabolism Hypoxia Lipoprotein lipase Male Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mice mMSCs Molecular Medicine Nerve Tissue Proteins - metabolism Nuclear Proteins - metabolism Protein binding Proteomics Regular Article Rodents Sca-1 Stem cells |
| title | Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential |
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