Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow–Derived CD34+ Stem Cells in a Nonhuman Primate Model
Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2005-03, Vol.23 (3), p.355-364 |
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| creator | Yoshioka, Toru Ageyama, Naohide Shibata, Hiroaki Yasu, Takanori Misawa, Yoshio Takeuchi, Koichi Matsui, Keiji Yamamoto, Keiji Terao, Keiji Shimada, Kazuyuki Ikeda, Uichi Ozawa, Keiya Hanazono, Yutaka |
| description | Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34+ cells were transplanted to the peri‐ischemic zone. To track the in vivo fate of transplanted cells, CD34+ cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline‐treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell–derived, GFP‐positive cells were found incorporated into the vascular structure, and GFP‐positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34+ cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell–derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells. |
| doi_str_mv | 10.1634/stemcells.2004-0200 |
| format | Article |
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In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34+ cells were transplanted to the peri‐ischemic zone. To track the in vivo fate of transplanted cells, CD34+ cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline‐treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell–derived, GFP‐positive cells were found incorporated into the vascular structure, and GFP‐positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34+ cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell–derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1634/stemcells.2004-0200</identifier><identifier>PMID: 15749930</identifier><language>eng</language><publisher>Bristol: John Wiley & Sons, Ltd</publisher><subject>Acute myocardial infarction ; Animals ; Antigens, CD34 - analysis ; Bone Marrow Transplantation ; Cell Differentiation - physiology ; Cell Movement - physiology ; Coronary Vessels - surgery ; Creatine Kinase - blood ; Disease Models, Animal ; Echocardiography ; Female ; Genetic marking ; Green Fluorescent Proteins - genetics ; Heart Function Tests ; Lentivirus - genetics ; Lentivirus vector ; Ligation ; Macaca fascicularis ; Male ; Myocardial Infarction - therapy ; Myocardium - metabolism ; Myocardium - pathology ; Neoangiogenesis ; Neovascularization, Physiologic - physiology ; Nonhuman primate ; Plasticity ; Regional Blood Flow - physiology ; Stem cell transplantation ; Stem Cells - chemistry ; Stem Cells - cytology ; Stem Cells - physiology ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Stem cells (Dayton, Ohio), 2005-03, Vol.23 (3), p.355-364</ispartof><rights>Copyright © 2005 AlphaMed Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4665-e20040387d4ec47d0a9cab908d94b0a1a44ff7f4f52750b8bdcdb8d9eb464f943</citedby><cites>FETCH-LOGICAL-c4665-e20040387d4ec47d0a9cab908d94b0a1a44ff7f4f52750b8bdcdb8d9eb464f943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15749930$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshioka, Toru</creatorcontrib><creatorcontrib>Ageyama, Naohide</creatorcontrib><creatorcontrib>Shibata, Hiroaki</creatorcontrib><creatorcontrib>Yasu, Takanori</creatorcontrib><creatorcontrib>Misawa, Yoshio</creatorcontrib><creatorcontrib>Takeuchi, Koichi</creatorcontrib><creatorcontrib>Matsui, Keiji</creatorcontrib><creatorcontrib>Yamamoto, Keiji</creatorcontrib><creatorcontrib>Terao, Keiji</creatorcontrib><creatorcontrib>Shimada, Kazuyuki</creatorcontrib><creatorcontrib>Ikeda, Uichi</creatorcontrib><creatorcontrib>Ozawa, Keiya</creatorcontrib><creatorcontrib>Hanazono, Yutaka</creatorcontrib><title>Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow–Derived CD34+ Stem Cells in a Nonhuman Primate Model</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34+ cells were transplanted to the peri‐ischemic zone. To track the in vivo fate of transplanted cells, CD34+ cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline‐treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell–derived, GFP‐positive cells were found incorporated into the vascular structure, and GFP‐positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34+ cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell–derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.</description><subject>Acute myocardial infarction</subject><subject>Animals</subject><subject>Antigens, CD34 - analysis</subject><subject>Bone Marrow Transplantation</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Movement - physiology</subject><subject>Coronary Vessels - surgery</subject><subject>Creatine Kinase - blood</subject><subject>Disease Models, Animal</subject><subject>Echocardiography</subject><subject>Female</subject><subject>Genetic marking</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Heart Function Tests</subject><subject>Lentivirus - genetics</subject><subject>Lentivirus vector</subject><subject>Ligation</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Neoangiogenesis</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>Nonhuman primate</subject><subject>Plasticity</subject><subject>Regional Blood Flow - physiology</subject><subject>Stem cell transplantation</subject><subject>Stem Cells - chemistry</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - physiology</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1O3DAUhS0E4mfKE1SqvGKDAs7kOonVVRl-JUKrMqwtJ74WQUk82BPQsOo79A15EmzNqN2ysX2v7zk-_gj5mrKTNM_g1C-xb7Dr_MmUMUhYWLfIfspBJCDScjucWZ4nnAmxRw68f2IsBV6Wu2Qv5QUIkbF98vYbF6p11Bp6MxjlmiVqWq1so5xux55WqFsVe_WKzp0a_KJTQ6zP7IC0Us7Z1_c_f8_RtS-hOzvP4Jjeh2R0FqPRdqCK3tnhcezVQH-5tg9utLIauy9kx6jO4-Fmn5CHy4v57Dq5_Xl1M_txmzSQ5zzB-DuWlYUGbKDQTIlG1YKVWkDNVKoAjCkMGD4tOKvLWje6DpdYQw5GQDYhR2vfhbPPI_ql7FsfwakB7ehlHliwMjwxIdl6sHHWe4dGLmJet5IpkxG5_IdcxlAyIg-qbxv7se5R_9dsGIeB7-uB17bD1Wc85f38opoGKefZB4Mmk6Y</recordid><startdate>200503</startdate><enddate>200503</enddate><creator>Yoshioka, Toru</creator><creator>Ageyama, Naohide</creator><creator>Shibata, Hiroaki</creator><creator>Yasu, Takanori</creator><creator>Misawa, Yoshio</creator><creator>Takeuchi, Koichi</creator><creator>Matsui, Keiji</creator><creator>Yamamoto, Keiji</creator><creator>Terao, Keiji</creator><creator>Shimada, Kazuyuki</creator><creator>Ikeda, Uichi</creator><creator>Ozawa, Keiya</creator><creator>Hanazono, Yutaka</creator><general>John Wiley & Sons, Ltd</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>7X8</scope></search><sort><creationdate>200503</creationdate><title>Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow–Derived CD34+ Stem Cells in a Nonhuman Primate Model</title><author>Yoshioka, Toru ; Ageyama, Naohide ; Shibata, Hiroaki ; Yasu, Takanori ; Misawa, Yoshio ; Takeuchi, Koichi ; Matsui, Keiji ; Yamamoto, Keiji ; Terao, Keiji ; Shimada, Kazuyuki ; Ikeda, Uichi ; Ozawa, Keiya ; Hanazono, Yutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4665-e20040387d4ec47d0a9cab908d94b0a1a44ff7f4f52750b8bdcdb8d9eb464f943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acute myocardial infarction</topic><topic>Animals</topic><topic>Antigens, CD34 - analysis</topic><topic>Bone Marrow Transplantation</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Movement - physiology</topic><topic>Coronary Vessels - surgery</topic><topic>Creatine Kinase - blood</topic><topic>Disease Models, Animal</topic><topic>Echocardiography</topic><topic>Female</topic><topic>Genetic marking</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Heart Function Tests</topic><topic>Lentivirus - genetics</topic><topic>Lentivirus vector</topic><topic>Ligation</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Myocardial Infarction - therapy</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Neoangiogenesis</topic><topic>Neovascularization, Physiologic - physiology</topic><topic>Nonhuman primate</topic><topic>Plasticity</topic><topic>Regional Blood Flow - physiology</topic><topic>Stem cell transplantation</topic><topic>Stem Cells - chemistry</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - physiology</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoshioka, Toru</creatorcontrib><creatorcontrib>Ageyama, Naohide</creatorcontrib><creatorcontrib>Shibata, Hiroaki</creatorcontrib><creatorcontrib>Yasu, Takanori</creatorcontrib><creatorcontrib>Misawa, Yoshio</creatorcontrib><creatorcontrib>Takeuchi, Koichi</creatorcontrib><creatorcontrib>Matsui, Keiji</creatorcontrib><creatorcontrib>Yamamoto, Keiji</creatorcontrib><creatorcontrib>Terao, Keiji</creatorcontrib><creatorcontrib>Shimada, Kazuyuki</creatorcontrib><creatorcontrib>Ikeda, Uichi</creatorcontrib><creatorcontrib>Ozawa, Keiya</creatorcontrib><creatorcontrib>Hanazono, Yutaka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshioka, Toru</au><au>Ageyama, Naohide</au><au>Shibata, Hiroaki</au><au>Yasu, Takanori</au><au>Misawa, Yoshio</au><au>Takeuchi, Koichi</au><au>Matsui, Keiji</au><au>Yamamoto, Keiji</au><au>Terao, Keiji</au><au>Shimada, Kazuyuki</au><au>Ikeda, Uichi</au><au>Ozawa, Keiya</au><au>Hanazono, Yutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow–Derived CD34+ Stem Cells in a Nonhuman Primate Model</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2005-03</date><risdate>2005</risdate><volume>23</volume><issue>3</issue><spage>355</spage><epage>364</epage><pages>355-364</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34+ cells were transplanted to the peri‐ischemic zone. To track the in vivo fate of transplanted cells, CD34+ cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline‐treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell–derived, GFP‐positive cells were found incorporated into the vascular structure, and GFP‐positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34+ cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell–derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.</abstract><cop>Bristol</cop><pub>John Wiley & Sons, Ltd</pub><pmid>15749930</pmid><doi>10.1634/stemcells.2004-0200</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acute myocardial infarction Animals Antigens, CD34 - analysis Bone Marrow Transplantation Cell Differentiation - physiology Cell Movement - physiology Coronary Vessels - surgery Creatine Kinase - blood Disease Models, Animal Echocardiography Female Genetic marking Green Fluorescent Proteins - genetics Heart Function Tests Lentivirus - genetics Lentivirus vector Ligation Macaca fascicularis Male Myocardial Infarction - therapy Myocardium - metabolism Myocardium - pathology Neoangiogenesis Neovascularization, Physiologic - physiology Nonhuman primate Plasticity Regional Blood Flow - physiology Stem cell transplantation Stem Cells - chemistry Stem Cells - cytology Stem Cells - physiology Vascular Endothelial Growth Factor A - metabolism |
| title | Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow–Derived CD34+ Stem Cells in a Nonhuman Primate Model |
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