Umbilical Cord Blood–derived Progenitor Cells Enhance Muscle Regeneration in Mouse Hindlimb Ischemia Model
Progenitor cell therapy is a potential new treatment option for ischemic conditions in the myocardium and skeletal muscles. However, it remains unclear whether umbilical cord blood (UCB)-derived progenitor cells can provide therapeutic effects in ischemic muscles and whether ex vivo gene transfer ca...
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| Veröffentlicht in: | Molecular therapy 2007-12, Vol.15 (12), p.2172-2177 |
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| creator | Koponen, Jonna K Kekarainen, Tuija Heinonen, Suvi E Laitinen, Anita Nystedt, Johanna Laine, Jarmo Ylä-Herttuala, Seppo |
| description | Progenitor cell therapy is a potential new treatment option for ischemic conditions in the myocardium and skeletal muscles. However, it remains unclear whether umbilical cord blood (UCB)-derived progenitor cells can provide therapeutic effects in ischemic muscles and whether ex vivo gene transfer can be used for improving the effect. In this study, the use of a lentiviral vector led to efficient transduction of both UCB-derived hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Our method resulted in a long-term transgene expression and did not alter the differentiation potential of either HSCs or MSCs. In addition, we studied the therapeutic potential of CD133+ and MSC progenitor cells transduced ex vivo with lentiviruses encoding the mature form of vascular endothelial growth factor D (VEGF-DΔNΔC) or the enhanced green fluorescent protein (eGFP) marker gene in a nude mouse model of skeletal muscle ischemia. Progenitor cells enhanced the regeneration of ischemic muscles without a detectable long-term engraftment of either CD133+ or MSC progenitor cells. Our results show that, rather than directly participating in angiogenesis or skeletal myogenesis, UCB-derived progenitor cells indirectly enhance the regenerative capacity of skeletal muscle after acute ischemic injury. However, VEGF-D gene transfer of progenitor cells did not improve the therapeutic effect in ischemic muscles. |
| doi_str_mv | 10.1038/sj.mt.6300302 |
| format | Article |
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However, it remains unclear whether umbilical cord blood (UCB)-derived progenitor cells can provide therapeutic effects in ischemic muscles and whether ex vivo gene transfer can be used for improving the effect. In this study, the use of a lentiviral vector led to efficient transduction of both UCB-derived hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Our method resulted in a long-term transgene expression and did not alter the differentiation potential of either HSCs or MSCs. In addition, we studied the therapeutic potential of CD133+ and MSC progenitor cells transduced ex vivo with lentiviruses encoding the mature form of vascular endothelial growth factor D (VEGF-DΔNΔC) or the enhanced green fluorescent protein (eGFP) marker gene in a nude mouse model of skeletal muscle ischemia. Progenitor cells enhanced the regeneration of ischemic muscles without a detectable long-term engraftment of either CD133+ or MSC progenitor cells. Our results show that, rather than directly participating in angiogenesis or skeletal myogenesis, UCB-derived progenitor cells indirectly enhance the regenerative capacity of skeletal muscle after acute ischemic injury. However, VEGF-D gene transfer of progenitor cells did not improve the therapeutic effect in ischemic muscles.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1038/sj.mt.6300302</identifier><identifier>PMID: 17878901</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Angina pectoris ; Angiogenesis ; Animals ; Antigens ; Cytokines ; Fetal Blood - cytology ; Gene therapy ; Hindlimb - blood supply ; Ischemia ; Ischemia - physiopathology ; Mice ; Mice, Nude ; Models, Animal ; Muscle, Skeletal - physiopathology ; Musculoskeletal system ; Regeneration ; Stem cells ; Stem Cells - cytology ; Umbilical cord ; Vascular endothelial growth factor ; Vectors (Biology)</subject><ispartof>Molecular therapy, 2007-12, Vol.15 (12), p.2172-2177</ispartof><rights>2007 The American Society of Gene Therapy</rights><rights>Copyright Nature Publishing Group Dec 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-283641561f417c80133cc2b065f12b50bde6b70907c9e1e7384ceb42d6bed05e3</citedby><cites>FETCH-LOGICAL-c406t-283641561f417c80133cc2b065f12b50bde6b70907c9e1e7384ceb42d6bed05e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17878901$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koponen, Jonna K</creatorcontrib><creatorcontrib>Kekarainen, Tuija</creatorcontrib><creatorcontrib>Heinonen, Suvi E</creatorcontrib><creatorcontrib>Laitinen, Anita</creatorcontrib><creatorcontrib>Nystedt, Johanna</creatorcontrib><creatorcontrib>Laine, Jarmo</creatorcontrib><creatorcontrib>Ylä-Herttuala, Seppo</creatorcontrib><title>Umbilical Cord Blood–derived Progenitor Cells Enhance Muscle Regeneration in Mouse Hindlimb Ischemia Model</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Progenitor cell therapy is a potential new treatment option for ischemic conditions in the myocardium and skeletal muscles. 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Our results show that, rather than directly participating in angiogenesis or skeletal myogenesis, UCB-derived progenitor cells indirectly enhance the regenerative capacity of skeletal muscle after acute ischemic injury. However, VEGF-D gene transfer of progenitor cells did not improve the therapeutic effect in ischemic muscles.</description><subject>Angina pectoris</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antigens</subject><subject>Cytokines</subject><subject>Fetal Blood - cytology</subject><subject>Gene therapy</subject><subject>Hindlimb - blood supply</subject><subject>Ischemia</subject><subject>Ischemia - physiopathology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Models, Animal</subject><subject>Muscle, Skeletal - physiopathology</subject><subject>Musculoskeletal system</subject><subject>Regeneration</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Umbilical cord</subject><subject>Vascular endothelial growth factor</subject><subject>Vectors (Biology)</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUFLHTEUhYMoaq1LtxIQ3M3rTTKTzCzbh62Cokhdh0lyn-aRmWgyI7jrf-g_7C9pyntYKHR1D_d-HA7nEnLCYMFAtJ_yejFMCykABPAdcsga3lQAvN5910wekA85r4tiTSf3yQFTrWo7YIckPAzGB2_7QJcxOfolxOh-_fjpMPlXdPQuxUcc_RQTXWIImV6MT_1okd7M2Qak91jOmPrJx5H6kd7EOSO99KMLfjD0KtsnHHxf9g7DR7K36kPG4-08Ig9fL74vL6vr229Xy8_Xla1BThVvhaxZI9mqZsq2wISwlhuQzYpx04BxKI2CDpTtkKESbW3R1NxJgw4aFEfkfOP7nOLLjHnSg8-2xO9HLPm0bBvBhegKePYPuI5zGks2zVTHJatVDYWqNpRNMeeEK_2c_NCnN81A_3mCzms9THr7hMKfbl1nM6D7S29bL4DaAFhKePWYdLYeS6vOJ7STdtH_x_o31t6WKQ</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>Koponen, Jonna K</creator><creator>Kekarainen, Tuija</creator><creator>Heinonen, Suvi E</creator><creator>Laitinen, Anita</creator><creator>Nystedt, Johanna</creator><creator>Laine, Jarmo</creator><creator>Ylä-Herttuala, Seppo</creator><general>Elsevier Inc</general><general>Elsevier Limited</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></search><sort><creationdate>20071201</creationdate><title>Umbilical Cord Blood–derived Progenitor Cells Enhance Muscle Regeneration in Mouse Hindlimb Ischemia Model</title><author>Koponen, Jonna K ; 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| subjects | Angina pectoris Angiogenesis Animals Antigens Cytokines Fetal Blood - cytology Gene therapy Hindlimb - blood supply Ischemia Ischemia - physiopathology Mice Mice, Nude Models, Animal Muscle, Skeletal - physiopathology Musculoskeletal system Regeneration Stem cells Stem Cells - cytology Umbilical cord Vascular endothelial growth factor Vectors (Biology) |
| title | Umbilical Cord Blood–derived Progenitor Cells Enhance Muscle Regeneration in Mouse Hindlimb Ischemia Model |
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