Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells
Lymphatic metastasis is one of the main prognostic factors concerning long‐term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not bee...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2018-08, Vol.22 (8), p.3740-3750 |
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| creator | Robering, Jan W. Weigand, Annika Pfuhlmann, Romy Horch, Raymund E. Beier, Justus P. Boos, Anja M. |
| description | Lymphatic metastasis is one of the main prognostic factors concerning long‐term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF‐C, bFGF, MSC‐conditioned medium (MSC‐CM) or by co‐culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary‐like structures was assessed by a tube formation assay on Matrigel®. The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC‐CM and by co‐culture with MSC. The effect of stimulation with MSC‐CM was stronger compared to stimulation with the growth factors VEGF‐C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF‐C, bFGF and by MSC‐CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes. |
| doi_str_mv | 10.1111/jcmm.13590 |
| format | Article |
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In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF‐C, bFGF, MSC‐conditioned medium (MSC‐CM) or by co‐culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary‐like structures was assessed by a tube formation assay on Matrigel®. The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC‐CM and by co‐culture with MSC. The effect of stimulation with MSC‐CM was stronger compared to stimulation with the growth factors VEGF‐C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF‐C, bFGF and by MSC‐CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.13590</identifier><identifier>PMID: 29752774</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Angiogenesis ; Assaying ; Cancer ; Capillary tubes ; Cell culture ; Cell migration ; Cell proliferation ; Collagen ; Conditioning ; Endothelial cells ; Fibrin ; Fibroblast growth factor 2 ; Gels ; Growth factors ; lymphangiogenesis ; lymphatic endothelial cells ; Medical prognosis ; Mesenchymal stem cells ; Mesenchyme ; Metastases ; Molecular chains ; Molecular modelling ; Original ; Secretome ; Spheroids ; Stem cells ; Stimulation ; Vascular endothelial growth factor ; Wound healing</subject><ispartof>Journal of cellular and molecular medicine, 2018-08, Vol.22 (8), p.3740-3750</ispartof><rights>2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF‐C, bFGF, MSC‐conditioned medium (MSC‐CM) or by co‐culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary‐like structures was assessed by a tube formation assay on Matrigel®. The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC‐CM and by co‐culture with MSC. The effect of stimulation with MSC‐CM was stronger compared to stimulation with the growth factors VEGF‐C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF‐C, bFGF and by MSC‐CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes.</description><subject>Angiogenesis</subject><subject>Assaying</subject><subject>Cancer</subject><subject>Capillary tubes</subject><subject>Cell culture</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Collagen</subject><subject>Conditioning</subject><subject>Endothelial cells</subject><subject>Fibrin</subject><subject>Fibroblast growth factor 2</subject><subject>Gels</subject><subject>Growth factors</subject><subject>lymphangiogenesis</subject><subject>lymphatic endothelial cells</subject><subject>Medical prognosis</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Molecular chains</subject><subject>Molecular modelling</subject><subject>Original</subject><subject>Secretome</subject><subject>Spheroids</subject><subject>Stem cells</subject><subject>Stimulation</subject><subject>Vascular endothelial growth factor</subject><subject>Wound healing</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc9LwzAUx4Mobk4v_gFS8CZs5ke7JBdBhj_Z8LKDt5Cmr1tH2tSkU_bf22116MVcEt778HmPfBG6JHhE2nO7MmU5IiyR-Aj1SSLoMJYsPu7eRDDRQ2chrDBmY8LkKepRyRPKedxH7zMIUJnlptQ2Cg2UkQFrQ1R7V7oGIrsp66WuFoVbQFWYbb0G3xQQIpd33aatQ5W5Zgm2aDU7wzk6ybUNcNHdAzR_fJhPnofTt6eXyf10aGJB8JBjJnTCRCYzlhKgGRghM4kp4aBB6DijOfAUgOZUJmOSGhJzzKXQHCeEsQG622vrdVpCZqBqvLaq9kWp_UY5Xai_napYqoX7VGOc4HhMW8F1J_DuYw2hUSu39lW7sqKYEywplrKlbvaU8S4ED_lhAsFqG4LahqB2IbTw1e-dDujPr7cA2QNfhYXNPyr1OpnN9tJvsvSUlA</recordid><startdate>201808</startdate><enddate>201808</enddate><creator>Robering, Jan W.</creator><creator>Weigand, Annika</creator><creator>Pfuhlmann, Romy</creator><creator>Horch, Raymund E.</creator><creator>Beier, Justus P.</creator><creator>Boos, Anja M.</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</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>FR3</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>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2533-5563</orcidid></search><sort><creationdate>201808</creationdate><title>Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells</title><author>Robering, Jan W. ; Weigand, Annika ; Pfuhlmann, Romy ; Horch, Raymund E. ; Beier, Justus P. ; Boos, Anja M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4810-7038a538d9d3b1e2dec89d90217eae8a4d2fe7bee2f29561bc1470798a705133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Angiogenesis</topic><topic>Assaying</topic><topic>Cancer</topic><topic>Capillary tubes</topic><topic>Cell culture</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Collagen</topic><topic>Conditioning</topic><topic>Endothelial cells</topic><topic>Fibrin</topic><topic>Fibroblast growth factor 2</topic><topic>Gels</topic><topic>Growth factors</topic><topic>lymphangiogenesis</topic><topic>lymphatic endothelial cells</topic><topic>Medical prognosis</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Molecular chains</topic><topic>Molecular modelling</topic><topic>Original</topic><topic>Secretome</topic><topic>Spheroids</topic><topic>Stem cells</topic><topic>Stimulation</topic><topic>Vascular endothelial growth factor</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Robering, Jan W.</creatorcontrib><creatorcontrib>Weigand, Annika</creatorcontrib><creatorcontrib>Pfuhlmann, Romy</creatorcontrib><creatorcontrib>Horch, Raymund E.</creatorcontrib><creatorcontrib>Beier, Justus P.</creatorcontrib><creatorcontrib>Boos, Anja M.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Robering, Jan W.</au><au>Weigand, Annika</au><au>Pfuhlmann, Romy</au><au>Horch, Raymund E.</au><au>Beier, Justus P.</au><au>Boos, Anja M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2018-08</date><risdate>2018</risdate><volume>22</volume><issue>8</issue><spage>3740</spage><epage>3750</epage><pages>3740-3750</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Lymphatic metastasis is one of the main prognostic factors concerning long‐term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF‐C, bFGF, MSC‐conditioned medium (MSC‐CM) or by co‐culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary‐like structures was assessed by a tube formation assay on Matrigel®. The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC‐CM and by co‐culture with MSC. The effect of stimulation with MSC‐CM was stronger compared to stimulation with the growth factors VEGF‐C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF‐C, bFGF and by MSC‐CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>29752774</pmid><doi>10.1111/jcmm.13590</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2533-5563</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Assaying Cancer Capillary tubes Cell culture Cell migration Cell proliferation Collagen Conditioning Endothelial cells Fibrin Fibroblast growth factor 2 Gels Growth factors lymphangiogenesis lymphatic endothelial cells Medical prognosis Mesenchymal stem cells Mesenchyme Metastases Molecular chains Molecular modelling Original Secretome Spheroids Stem cells Stimulation Vascular endothelial growth factor Wound healing |
| title | Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells |
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