Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats
In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We...
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| Veröffentlicht in: | Journal of cellular physiology 2019-02, Vol.234 (2), p.1354-1368 |
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| creator | Jiang, Run‐Hao Wu, Chen‐Jiang Xu, Xiao‐Quan Lu, Shan‐Shan Zu, Qing‐Quan Zhao, Lin‐Bo Wang, Jun Liu, Sheng Shi, Hai‐Bin |
| description | In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label‐free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label‐free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.
Conditioned medium constitutes a therapeutic effect on stroke. Paracrine actions of bone marrow mesenchymal stromal cell are enhanced by hypoxic preconditioning. Apoptosis and neovascularization are involved in this beneficial effect. |
| doi_str_mv | 10.1002/jcp.26931 |
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Conditioned medium constitutes a therapeutic effect on stroke. Paracrine actions of bone marrow mesenchymal stromal cell are enhanced by hypoxic preconditioning. Apoptosis and neovascularization are involved in this beneficial effect.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.26931</identifier><identifier>PMID: 30076722</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis ; Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Attenuation ; Bone marrow ; Bone Marrow Cells - metabolism ; Brain ; Brain - drug effects ; Brain - metabolism ; Brain - pathology ; Brain - physiopathology ; Brain injury ; Cell Hypoxia ; Cells, Cultured ; Cerebral blood flow ; conditioned medium (CM) ; Conditioning ; Culture Media, Conditioned - metabolism ; Culture Media, Conditioned - pharmacology ; Cytokines ; Cytokines - metabolism ; Disease Models, Animal ; Growth factors ; Hypoxia ; hypoxic ; Infarction, Middle Cerebral Artery - drug therapy ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - pathology ; Infarction, Middle Cerebral Artery - physiopathology ; Ischemia ; Male ; Mesenchymal stem cells ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; Neovascularization, Physiologic - drug effects ; Neuroprotective Agents - metabolism ; Neuroprotective Agents - pharmacology ; Occlusion ; Phosphatidylinositol 3-Kinase - metabolism ; Phosphorylation ; Preconditioning ; Proteins ; Proteomics ; Proto-Oncogene Proteins c-akt - metabolism ; Rats ; Rats, Sprague-Dawley ; Recovery ; Recovery of Function ; Secretome ; stem cell ; Stroke ; Stromal cells</subject><ispartof>Journal of cellular physiology, 2019-02, Vol.234 (2), p.1354-1368</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3531-e123e34ee55d712b662cce5fe0002676d4310195337b941f1d1276a44c89aafe3</citedby><cites>FETCH-LOGICAL-c3531-e123e34ee55d712b662cce5fe0002676d4310195337b941f1d1276a44c89aafe3</cites><orcidid>0000-0003-1293-5789</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.26931$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.26931$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30076722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Run‐Hao</creatorcontrib><creatorcontrib>Wu, Chen‐Jiang</creatorcontrib><creatorcontrib>Xu, Xiao‐Quan</creatorcontrib><creatorcontrib>Lu, Shan‐Shan</creatorcontrib><creatorcontrib>Zu, Qing‐Quan</creatorcontrib><creatorcontrib>Zhao, Lin‐Bo</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Liu, Sheng</creatorcontrib><creatorcontrib>Shi, Hai‐Bin</creatorcontrib><title>Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label‐free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label‐free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.
Conditioned medium constitutes a therapeutic effect on stroke. Paracrine actions of bone marrow mesenchymal stromal cell are enhanced by hypoxic preconditioning. Apoptosis and neovascularization are involved in this beneficial effect.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Attenuation</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain - physiopathology</subject><subject>Brain injury</subject><subject>Cell Hypoxia</subject><subject>Cells, Cultured</subject><subject>Cerebral blood flow</subject><subject>conditioned medium (CM)</subject><subject>Conditioning</subject><subject>Culture Media, Conditioned - metabolism</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Growth factors</subject><subject>Hypoxia</subject><subject>hypoxic</subject><subject>Infarction, Middle Cerebral Artery - drug therapy</subject><subject>Infarction, Middle Cerebral Artery - metabolism</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Infarction, Middle Cerebral Artery - physiopathology</subject><subject>Ischemia</subject><subject>Male</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchyme</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Neuroprotective Agents - metabolism</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Occlusion</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Phosphorylation</subject><subject>Preconditioning</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recovery</subject><subject>Recovery of Function</subject><subject>Secretome</subject><subject>stem cell</subject><subject>Stroke</subject><subject>Stromal cells</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUtLxDAUhYMoOj4W_gEJuNFFnTya1ixlUEcRdKHrkElvNWPbjEmrzr_36qgLwUW4hPNxOPdcQvY5O-GMifHcLU5EoSVfIyPOdJnlhRLrZIQaz7TK-RbZTmnOGNNayk2yJRkri1KIEXmdLhfh3TvqQlf53ocOKtpC5YeWVhD9K37rGFo6Q4W2NsbwhnqCzj0tW9vQ1KOK00HTJLqIoQfXJ2ofre9ST31yT9Ci_yf3DNR3NNo-7ZKN2jYJ9r7nDnm4OL-fTLOb28urydlN5qSSPAMuJMgcQKmq5GJWFMI5UDXgKqIoiyqXnHGtpCxnOuc1r7goC5vn7lRbW4PcIUcrXwz2MkDqTYuJMKrtIAzJCHYqS3xCIXr4B52HIXaYzgguldJayByp4xXlYkgpQm0W0WMtS8OZ-TyGwWOYr2Mge_DtOMyw0l_yp30ExivgzTew_N_JXE_uVpYfHDSUHg</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Jiang, Run‐Hao</creator><creator>Wu, Chen‐Jiang</creator><creator>Xu, Xiao‐Quan</creator><creator>Lu, Shan‐Shan</creator><creator>Zu, Qing‐Quan</creator><creator>Zhao, Lin‐Bo</creator><creator>Wang, Jun</creator><creator>Liu, Sheng</creator><creator>Shi, Hai‐Bin</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1293-5789</orcidid></search><sort><creationdate>201902</creationdate><title>Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats</title><author>Jiang, Run‐Hao ; 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Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label‐free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label‐free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.
Conditioned medium constitutes a therapeutic effect on stroke. Paracrine actions of bone marrow mesenchymal stromal cell are enhanced by hypoxic preconditioning. Apoptosis and neovascularization are involved in this beneficial effect.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30076722</pmid><doi>10.1002/jcp.26931</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-1293-5789</orcidid></addata></record> |
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| subjects | Angiogenesis Animals Antioxidants Apoptosis Apoptosis - drug effects Attenuation Bone marrow Bone Marrow Cells - metabolism Brain Brain - drug effects Brain - metabolism Brain - pathology Brain - physiopathology Brain injury Cell Hypoxia Cells, Cultured Cerebral blood flow conditioned medium (CM) Conditioning Culture Media, Conditioned - metabolism Culture Media, Conditioned - pharmacology Cytokines Cytokines - metabolism Disease Models, Animal Growth factors Hypoxia hypoxic Infarction, Middle Cerebral Artery - drug therapy Infarction, Middle Cerebral Artery - metabolism Infarction, Middle Cerebral Artery - pathology Infarction, Middle Cerebral Artery - physiopathology Ischemia Male Mesenchymal stem cells Mesenchymal Stem Cells - metabolism Mesenchyme Neovascularization, Physiologic - drug effects Neuroprotective Agents - metabolism Neuroprotective Agents - pharmacology Occlusion Phosphatidylinositol 3-Kinase - metabolism Phosphorylation Preconditioning Proteins Proteomics Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Sprague-Dawley Recovery Recovery of Function Secretome stem cell Stroke Stromal cells |
| title | Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats |
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