Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats
Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. A DCM mo...
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description | Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.
A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy.
Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity.
Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium. |
doi_str_mv | 10.1186/s13287-017-0472-y |
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A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy.
Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity.
Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.</description><identifier>ISSN: 1757-6512</identifier><identifier>EISSN: 1757-6512</identifier><identifier>DOI: 10.1186/s13287-017-0472-y</identifier><identifier>PMID: 28129792</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Cardiomyopathy, Dilated - genetics ; Cardiomyopathy, Dilated - metabolism ; Cardiomyopathy, Dilated - pathology ; Cardiomyopathy, Dilated - therapy ; Care and treatment ; Congestive cardiomyopathy ; Dosage and administration ; Electron microscopy ; Fetal Blood - cytology ; Fetal Blood - metabolism ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor - blood ; Granulocyte-Macrophage Colony-Stimulating Factor - genetics ; Hepatocyte Growth Factor - blood ; Hepatocyte Growth Factor - genetics ; Humans ; Injections, Intramuscular ; Insulin-Like Growth Factor I - genetics ; Insulin-Like Growth Factor I - metabolism ; Intramuscular injections ; Leukemia Inhibitory Factor - blood ; Leukemia Inhibitory Factor - genetics ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Mitochondria, Heart - metabolism ; Mitochondria, Heart - pathology ; Myocardium - metabolism ; Myocardium - pathology ; Natriuretic Peptide, Brain - blood ; Natriuretic Peptide, Brain - genetics ; Rats ; Rats, Sprague-Dawley ; Recovery of Function - physiology ; Stem cells ; Stroke Volume - physiology ; Transplantation, Heterologous ; Troponin I - blood ; Troponin I - genetics ; Umbilical cord ; Vascular Endothelial Growth Factor A - blood ; Vascular Endothelial Growth Factor A - genetics ; Ventricular Function, Left - physiology</subject><ispartof>Stem cell research & therapy, 2017-01, Vol.8 (1), p.18-18, Article 18</ispartof><rights>COPYRIGHT 2017 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2017</rights><rights>The Author(s). 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c625t-dbcf3a94ef8f21a77bd556303abd61af0a2286194950932cfd3d592f7805cbac3</citedby><cites>FETCH-LOGICAL-c625t-dbcf3a94ef8f21a77bd556303abd61af0a2286194950932cfd3d592f7805cbac3</cites><orcidid>0000-0002-5244-272X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5273808/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5273808/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28129792$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Chenggang</creatorcontrib><creatorcontrib>Hou, Xu</creatorcontrib><creatorcontrib>Wang, Benzhen</creatorcontrib><creatorcontrib>Chi, Jingwei</creatorcontrib><creatorcontrib>Jiang, Yanjie</creatorcontrib><creatorcontrib>Zhang, Caining</creatorcontrib><creatorcontrib>Li, Zipu</creatorcontrib><title>Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats</title><title>Stem cell research & therapy</title><addtitle>Stem Cell Res Ther</addtitle><description>Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.
A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy.
Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity.
Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.</description><subject>Animals</subject><subject>Cardiomyopathy, Dilated - genetics</subject><subject>Cardiomyopathy, Dilated - metabolism</subject><subject>Cardiomyopathy, Dilated - pathology</subject><subject>Cardiomyopathy, Dilated - therapy</subject><subject>Care and treatment</subject><subject>Congestive cardiomyopathy</subject><subject>Dosage and administration</subject><subject>Electron microscopy</subject><subject>Fetal Blood - cytology</subject><subject>Fetal Blood - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - blood</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</subject><subject>Hepatocyte Growth Factor - blood</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Humans</subject><subject>Injections, Intramuscular</subject><subject>Insulin-Like Growth Factor I - genetics</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Intramuscular injections</subject><subject>Leukemia Inhibitory Factor - blood</subject><subject>Leukemia Inhibitory Factor - genetics</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Mitochondria, Heart - metabolism</subject><subject>Mitochondria, Heart - pathology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Natriuretic Peptide, Brain - blood</subject><subject>Natriuretic Peptide, Brain - genetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recovery of Function - physiology</subject><subject>Stem cells</subject><subject>Stroke Volume - physiology</subject><subject>Transplantation, Heterologous</subject><subject>Troponin I - blood</subject><subject>Troponin I - genetics</subject><subject>Umbilical cord</subject><subject>Vascular Endothelial Growth Factor A - blood</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Ventricular Function, Left - physiology</subject><issn>1757-6512</issn><issn>1757-6512</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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>eNptkl2L1DAUhoso7rLuD_BGAoLoRdckbZr2RlgWPwYWBD-uQ5qPaYYmGZN0sL_Av23qrMNUbCgpOc_7lpPzFsVzBG8Qapu3EVW4pSVE-a0pLudHxSWihJYNQfjx2fdFcR3jDuanqiBs6qfFBW4R7miHL4tfG5cCt1MU08gDMG6nRDLeAa_BMFnuwGR7MxrBRyB8kKVUwRyUBFZF5cQw21yISVkg1DhGYOw--IOKQPAgDRdAT-5oaByQZuQpa__UvJ39nqdhBoGn-Kx4ovkY1fXDflV8__D-292n8v7zx83d7X0pGkxSKXuhK97VSrcaI05pLwlpKljxXjaIa8gxbhvU1R2BXYWFlpUkHda0hUT0XFRXxbuj737qrZJCLe2PbB-M5WFmnhu2rjgzsK0_MIJp1cI2G7x-MAj-x6RiYtbEpXfulJ8iy6PBtIGU1hl9-Q-681Nwub2FIg3saB7JidryUTHjtM__FYspu61phwiqCcrUzX-ovKSyRnintMnnK8GblSAzSf1MWz7FyDZfv6zZV2fsoPiYhujHaZlbXIPoCIrgYwxKny4OQbakkh1TyXIq2ZJKNmfNi_MbPyn-ZrD6DW8m3o8</recordid><startdate>20170128</startdate><enddate>20170128</enddate><creator>Mao, Chenggang</creator><creator>Hou, Xu</creator><creator>Wang, Benzhen</creator><creator>Chi, Jingwei</creator><creator>Jiang, Yanjie</creator><creator>Zhang, Caining</creator><creator>Li, Zipu</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</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>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5244-272X</orcidid></search><sort><creationdate>20170128</creationdate><title>Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats</title><author>Mao, Chenggang ; Hou, Xu ; Wang, Benzhen ; Chi, Jingwei ; Jiang, Yanjie ; Zhang, Caining ; Li, Zipu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c625t-dbcf3a94ef8f21a77bd556303abd61af0a2286194950932cfd3d592f7805cbac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Cardiomyopathy, Dilated - genetics</topic><topic>Cardiomyopathy, Dilated - metabolism</topic><topic>Cardiomyopathy, Dilated - pathology</topic><topic>Cardiomyopathy, Dilated - therapy</topic><topic>Care and treatment</topic><topic>Congestive cardiomyopathy</topic><topic>Dosage and administration</topic><topic>Electron microscopy</topic><topic>Fetal Blood - cytology</topic><topic>Fetal Blood - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - blood</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</topic><topic>Hepatocyte Growth Factor - blood</topic><topic>Hepatocyte Growth Factor - genetics</topic><topic>Humans</topic><topic>Injections, Intramuscular</topic><topic>Insulin-Like Growth Factor I - genetics</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Intramuscular injections</topic><topic>Leukemia Inhibitory Factor - blood</topic><topic>Leukemia Inhibitory Factor - genetics</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Mitochondria, Heart - metabolism</topic><topic>Mitochondria, Heart - pathology</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Natriuretic Peptide, Brain - blood</topic><topic>Natriuretic Peptide, Brain - genetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Recovery of Function - physiology</topic><topic>Stem cells</topic><topic>Stroke Volume - physiology</topic><topic>Transplantation, Heterologous</topic><topic>Troponin I - blood</topic><topic>Troponin I - genetics</topic><topic>Umbilical cord</topic><topic>Vascular Endothelial Growth Factor A - blood</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Ventricular Function, Left - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Chenggang</creatorcontrib><creatorcontrib>Hou, Xu</creatorcontrib><creatorcontrib>Wang, Benzhen</creatorcontrib><creatorcontrib>Chi, Jingwei</creatorcontrib><creatorcontrib>Jiang, Yanjie</creatorcontrib><creatorcontrib>Zhang, Caining</creatorcontrib><creatorcontrib>Li, Zipu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>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>Biological Science Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cell research & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao, Chenggang</au><au>Hou, Xu</au><au>Wang, Benzhen</au><au>Chi, Jingwei</au><au>Jiang, Yanjie</au><au>Zhang, Caining</au><au>Li, Zipu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats</atitle><jtitle>Stem cell research & therapy</jtitle><addtitle>Stem Cell Res Ther</addtitle><date>2017-01-28</date><risdate>2017</risdate><volume>8</volume><issue>1</issue><spage>18</spage><epage>18</epage><pages>18-18</pages><artnum>18</artnum><issn>1757-6512</issn><eissn>1757-6512</eissn><abstract>Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.
A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy.
Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity.
Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>28129792</pmid><doi>10.1186/s13287-017-0472-y</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5244-272X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cardiomyopathy, Dilated - genetics Cardiomyopathy, Dilated - metabolism Cardiomyopathy, Dilated - pathology Cardiomyopathy, Dilated - therapy Care and treatment Congestive cardiomyopathy Dosage and administration Electron microscopy Fetal Blood - cytology Fetal Blood - metabolism Gene Expression Regulation Granulocyte-Macrophage Colony-Stimulating Factor - blood Granulocyte-Macrophage Colony-Stimulating Factor - genetics Hepatocyte Growth Factor - blood Hepatocyte Growth Factor - genetics Humans Injections, Intramuscular Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - metabolism Intramuscular injections Leukemia Inhibitory Factor - blood Leukemia Inhibitory Factor - genetics Male Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mitochondria, Heart - metabolism Mitochondria, Heart - pathology Myocardium - metabolism Myocardium - pathology Natriuretic Peptide, Brain - blood Natriuretic Peptide, Brain - genetics Rats Rats, Sprague-Dawley Recovery of Function - physiology Stem cells Stroke Volume - physiology Transplantation, Heterologous Troponin I - blood Troponin I - genetics Umbilical cord Vascular Endothelial Growth Factor A - blood Vascular Endothelial Growth Factor A - genetics Ventricular Function, Left - physiology |
title | Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats |
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