Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis
Using stem cell–conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the med...
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| Veröffentlicht in: | Molecular therapy 2014-04, Vol.22 (4), p.862-872 |
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| creator | Bhang, Suk Ho Lee, Seahyoung Shin, Jung-Youn Lee, Tae-Jin Jang, Hyeon-Ki Kim, Byung-Soo |
| description | Using stem cell–conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the medium are not for human use. We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34+/PTPRC− (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy. |
| doi_str_mv | 10.1038/mt.2013.301 |
| format | Article |
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We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34+/PTPRC− (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1038/mt.2013.301</identifier><identifier>PMID: 24413377</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adipose Tissue - cytology ; Amino acids ; Angiogenesis ; Animals ; Apoptosis - genetics ; Bioengineering ; Bone marrow ; Cell Culture Techniques ; Cell growth ; Chemokines ; Culture Media, Conditioned ; Cytokines ; Growth factors ; Humans ; Ischemia ; Ligands ; Mice ; Original ; Stem cell transplantation ; Stem Cells - cytology</subject><ispartof>Molecular therapy, 2014-04, Vol.22 (4), p.862-872</ispartof><rights>2014 The American Society of Gene & Cell Therapy</rights><rights>Copyright Nature Publishing Group Apr 2014</rights><rights>Copyright © 2014 The American Society of Gene & Cell Therapy 2014 The American Society of Gene & Cell Therapy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-a92aa8e47ad2764dd2cc91201e56498fd6744fa9715d7df628d0a8640f6dd9043</citedby><cites>FETCH-LOGICAL-c554t-a92aa8e47ad2764dd2cc91201e56498fd6744fa9715d7df628d0a8640f6dd9043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982496/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982496/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24413377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhang, Suk Ho</creatorcontrib><creatorcontrib>Lee, Seahyoung</creatorcontrib><creatorcontrib>Shin, Jung-Youn</creatorcontrib><creatorcontrib>Lee, Tae-Jin</creatorcontrib><creatorcontrib>Jang, Hyeon-Ki</creatorcontrib><creatorcontrib>Kim, Byung-Soo</creatorcontrib><title>Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Using stem cell–conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the medium are not for human use. 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The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.</description><subject>Adipose Tissue - cytology</subject><subject>Amino acids</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Bioengineering</subject><subject>Bone marrow</subject><subject>Cell Culture Techniques</subject><subject>Cell growth</subject><subject>Chemokines</subject><subject>Culture Media, Conditioned</subject><subject>Cytokines</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Ligands</subject><subject>Mice</subject><subject>Original</subject><subject>Stem cell transplantation</subject><subject>Stem Cells - cytology</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkUuLFDEUhQtRnIeu3EvAjSDVJqk8qjZCU4wzwoig4zrE5KYnQ1XSJqmW-fem6bFREVzlkvtxuOecpnlB8Irgrn87lxXFpFt1mDxqTgmnvMWYssfHmYiT5iznuzoRPoinzQlljHSdlKfNjwvnvNHGxyUjHSwaJx_qxzTdo88wwU6HgsYYrC8-BrDoI1i_zCg6dLXMOqC19duYobWQ_K7uvxSY0QjTlJGLCd3cQtJbWIo3aB02Pm4gQPb5WfPE6SnD84f3vPn6_uJmvGqvP11-GNfXreGclVYPVOsemNSWSsGspcYMpNoFLtjQOyskY04PknArrRO0t1j3gmEnrB0w686bdwfd7fJtBmsglKQntU1-1uleRe3Vn5vgb9Um7lQ39JQNogq8fhBI8fsCuajZZ1P96QA1M0WE7BjGuJP_Rzmh1dVA9me9-gu9i0sKNQlFZAUqJPbUmwNlUsw5gTveTbDad6_movbdq9p9pV_-bvXI_iq7AvwAQA185yGpbDwEUxtNYIqy0f9T-Cec2rzE</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Bhang, Suk Ho</creator><creator>Lee, Seahyoung</creator><creator>Shin, Jung-Youn</creator><creator>Lee, Tae-Jin</creator><creator>Jang, Hyeon-Ki</creator><creator>Kim, Byung-Soo</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20140401</creationdate><title>Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis</title><author>Bhang, Suk Ho ; 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We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34+/PTPRC− (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24413377</pmid><doi>10.1038/mt.2013.301</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular therapy, 2014-04, Vol.22 (4), p.862-872 |
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| subjects | Adipose Tissue - cytology Amino acids Angiogenesis Animals Apoptosis - genetics Bioengineering Bone marrow Cell Culture Techniques Cell growth Chemokines Culture Media, Conditioned Cytokines Growth factors Humans Ischemia Ligands Mice Original Stem cell transplantation Stem Cells - cytology |
| title | Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis |
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