Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats
•Gene therapy is an innovative approach to treat spinal cord injury (SCI).•Cell-mediated gene therapy in SCI seems to be more effective then direct gene delivery.•Umbilical cord blood cells (UCBCs) are effective carriers of therapeutic genes.•Triple-gene therapy with intra-thecal delivery has been f...
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| Veröffentlicht in: | Brain research bulletin 2017-06, Vol.132, p.44-52 |
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| creator | Islamov, Rustem Robertovich Izmailov, Andrey Alexandrovich Sokolov, Mikhail Evgenyevich Fadeev, Philip Olegovich Bashirov, Farid Vagizovich Eremeev, Anton Alexandrovich Shaymardanova, Gulnara Ferdinantovna Shmarov, Maxim Michaylovich Naroditskiy, Boris Savelyevich Chelyshev, Yuri Alexandrovich Lavrov, Igor Aleksandrovich Palotás, András |
| description | •Gene therapy is an innovative approach to treat spinal cord injury (SCI).•Cell-mediated gene therapy in SCI seems to be more effective then direct gene delivery.•Umbilical cord blood cells (UCBCs) are effective carriers of therapeutic genes.•Triple-gene therapy with intra-thecal delivery has been found to be effective in SCI.•Genetic modification of UCBCs with therapeutic genes promotes healing processes in SCI.
Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI. |
| doi_str_mv | 10.1016/j.brainresbull.2017.05.005 |
| format | Article |
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Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI.</description><identifier>ISSN: 0361-9230</identifier><identifier>EISSN: 1873-2747</identifier><identifier>DOI: 10.1016/j.brainresbull.2017.05.005</identifier><identifier>PMID: 28529158</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adeno-virus ; Adenoviridae - genetics ; Angiogenin ; Animals ; CD56 Antigen - genetics ; CD56 Antigen - metabolism ; Cord Blood Stem Cell Transplantation ; Disease Models, Animal ; Escherichia coli ; Female ; Fetal Blood - cytology ; Genetic Therapy - methods ; Genetic Vectors ; Glial Cell Line-Derived Neurotrophic Factor - genetics ; Glial Cell Line-Derived Neurotrophic Factor - metabolism ; Glial cell-derived neurotrophic factor ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; HEK293 Cells ; Human umbilical cord blood mononuclear cell ; Humans ; Injections, Spinal ; Neural cell adhesion molecule ; Rats, Wistar ; Ribonuclease, Pancreatic - genetics ; Ribonuclease, Pancreatic - metabolism ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology ; Spinal Cord Injuries - therapy ; Spinal cord injury ; Spinal Cord Regeneration - physiology ; Transduction, Genetic ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; Vector</subject><ispartof>Brain research bulletin, 2017-06, Vol.132, p.44-52</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-b4f9a2be205f76ba3dc1d79feebda1c47f26b8854fb96093b432e92879daa9f73</citedby><cites>FETCH-LOGICAL-c380t-b4f9a2be205f76ba3dc1d79feebda1c47f26b8854fb96093b432e92879daa9f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0361923017300953$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28529158$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Islamov, Rustem Robertovich</creatorcontrib><creatorcontrib>Izmailov, Andrey Alexandrovich</creatorcontrib><creatorcontrib>Sokolov, Mikhail Evgenyevich</creatorcontrib><creatorcontrib>Fadeev, Philip Olegovich</creatorcontrib><creatorcontrib>Bashirov, Farid Vagizovich</creatorcontrib><creatorcontrib>Eremeev, Anton Alexandrovich</creatorcontrib><creatorcontrib>Shaymardanova, Gulnara Ferdinantovna</creatorcontrib><creatorcontrib>Shmarov, Maxim Michaylovich</creatorcontrib><creatorcontrib>Naroditskiy, Boris Savelyevich</creatorcontrib><creatorcontrib>Chelyshev, Yuri Alexandrovich</creatorcontrib><creatorcontrib>Lavrov, Igor Aleksandrovich</creatorcontrib><creatorcontrib>Palotás, András</creatorcontrib><title>Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats</title><title>Brain research bulletin</title><addtitle>Brain Res Bull</addtitle><description>•Gene therapy is an innovative approach to treat spinal cord injury (SCI).•Cell-mediated gene therapy in SCI seems to be more effective then direct gene delivery.•Umbilical cord blood cells (UCBCs) are effective carriers of therapeutic genes.•Triple-gene therapy with intra-thecal delivery has been found to be effective in SCI.•Genetic modification of UCBCs with therapeutic genes promotes healing processes in SCI.
Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI.</description><subject>Adeno-virus</subject><subject>Adenoviridae - genetics</subject><subject>Angiogenin</subject><subject>Animals</subject><subject>CD56 Antigen - genetics</subject><subject>CD56 Antigen - metabolism</subject><subject>Cord Blood Stem Cell Transplantation</subject><subject>Disease Models, Animal</subject><subject>Escherichia coli</subject><subject>Female</subject><subject>Fetal Blood - cytology</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - genetics</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - metabolism</subject><subject>Glial cell-derived neurotrophic factor</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>HEK293 Cells</subject><subject>Human umbilical cord blood mononuclear cell</subject><subject>Humans</subject><subject>Injections, Spinal</subject><subject>Neural cell adhesion molecule</subject><subject>Rats, Wistar</subject><subject>Ribonuclease, Pancreatic - genetics</subject><subject>Ribonuclease, Pancreatic - metabolism</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal Cord Injuries - therapy</subject><subject>Spinal cord injury</subject><subject>Spinal Cord Regeneration - physiology</subject><subject>Transduction, Genetic</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vector</subject><issn>0361-9230</issn><issn>1873-2747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE9P3DAQxS1EBduFr4CsnnpJOraTOO6tgqWttFIvReJm-c8YvMomqZ0g8e3JsrTqkdNoRu_Nm_kR8olByYA1X3alTSb2CbOdu67kwGQJdQlQn5AVa6UouKzkKVmBaFihuIBz8jHnHQA0bd2ckXPe1lyxul2R-82T6WYzxaGnQ6A-JnQTNb2nDruu2KOPZkJPpxTHDosH7JFOj5jM-ExjT_MYe9NRNyS_tLs5vU6TmfIF-RBMl_Hyra7J3e3m9_WPYvvr-8_rb9vCiRamwlZBGW6RQx1kY43wjnmpAqL1hrlKBt7Ytq2rYFUDSthKcFS8lcobo4IUa_L5uHdMw58Z86T3MR9uNz0Oc9ZMAROgmOCL9OtR6tKQc8KgxxT3Jj1rBvpAVu_0_2T1gayGWi9kF_PVW85sFyr_rH9RLoKbowCXb58iJp1dxN7hkan2Q3xPzguHlpJ3</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Islamov, Rustem Robertovich</creator><creator>Izmailov, Andrey Alexandrovich</creator><creator>Sokolov, Mikhail Evgenyevich</creator><creator>Fadeev, Philip Olegovich</creator><creator>Bashirov, Farid Vagizovich</creator><creator>Eremeev, Anton Alexandrovich</creator><creator>Shaymardanova, Gulnara Ferdinantovna</creator><creator>Shmarov, Maxim Michaylovich</creator><creator>Naroditskiy, Boris Savelyevich</creator><creator>Chelyshev, Yuri Alexandrovich</creator><creator>Lavrov, Igor Aleksandrovich</creator><creator>Palotás, András</creator><general>Elsevier Inc</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>201706</creationdate><title>Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats</title><author>Islamov, Rustem Robertovich ; Izmailov, Andrey Alexandrovich ; Sokolov, Mikhail Evgenyevich ; Fadeev, Philip Olegovich ; Bashirov, Farid Vagizovich ; Eremeev, Anton Alexandrovich ; Shaymardanova, Gulnara Ferdinantovna ; Shmarov, Maxim Michaylovich ; Naroditskiy, Boris Savelyevich ; Chelyshev, Yuri Alexandrovich ; Lavrov, Igor Aleksandrovich ; Palotás, András</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-b4f9a2be205f76ba3dc1d79feebda1c47f26b8854fb96093b432e92879daa9f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adeno-virus</topic><topic>Adenoviridae - genetics</topic><topic>Angiogenin</topic><topic>Animals</topic><topic>CD56 Antigen - genetics</topic><topic>CD56 Antigen - metabolism</topic><topic>Cord Blood Stem Cell Transplantation</topic><topic>Disease Models, Animal</topic><topic>Escherichia coli</topic><topic>Female</topic><topic>Fetal Blood - cytology</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - genetics</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - metabolism</topic><topic>Glial cell-derived neurotrophic factor</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>HEK293 Cells</topic><topic>Human umbilical cord blood mononuclear cell</topic><topic>Humans</topic><topic>Injections, Spinal</topic><topic>Neural cell adhesion molecule</topic><topic>Rats, Wistar</topic><topic>Ribonuclease, Pancreatic - genetics</topic><topic>Ribonuclease, Pancreatic - metabolism</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal Cord Injuries - therapy</topic><topic>Spinal cord injury</topic><topic>Spinal Cord Regeneration - physiology</topic><topic>Transduction, Genetic</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Vector</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Islamov, Rustem Robertovich</creatorcontrib><creatorcontrib>Izmailov, Andrey Alexandrovich</creatorcontrib><creatorcontrib>Sokolov, Mikhail Evgenyevich</creatorcontrib><creatorcontrib>Fadeev, Philip Olegovich</creatorcontrib><creatorcontrib>Bashirov, Farid Vagizovich</creatorcontrib><creatorcontrib>Eremeev, Anton Alexandrovich</creatorcontrib><creatorcontrib>Shaymardanova, Gulnara Ferdinantovna</creatorcontrib><creatorcontrib>Shmarov, Maxim Michaylovich</creatorcontrib><creatorcontrib>Naroditskiy, Boris Savelyevich</creatorcontrib><creatorcontrib>Chelyshev, Yuri Alexandrovich</creatorcontrib><creatorcontrib>Lavrov, Igor Aleksandrovich</creatorcontrib><creatorcontrib>Palotás, András</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>Brain research bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Islamov, Rustem Robertovich</au><au>Izmailov, Andrey Alexandrovich</au><au>Sokolov, Mikhail Evgenyevich</au><au>Fadeev, Philip Olegovich</au><au>Bashirov, Farid Vagizovich</au><au>Eremeev, Anton Alexandrovich</au><au>Shaymardanova, Gulnara Ferdinantovna</au><au>Shmarov, Maxim Michaylovich</au><au>Naroditskiy, Boris Savelyevich</au><au>Chelyshev, Yuri Alexandrovich</au><au>Lavrov, Igor Aleksandrovich</au><au>Palotás, András</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats</atitle><jtitle>Brain research bulletin</jtitle><addtitle>Brain Res Bull</addtitle><date>2017-06</date><risdate>2017</risdate><volume>132</volume><spage>44</spage><epage>52</epage><pages>44-52</pages><issn>0361-9230</issn><eissn>1873-2747</eissn><abstract>•Gene therapy is an innovative approach to treat spinal cord injury (SCI).•Cell-mediated gene therapy in SCI seems to be more effective then direct gene delivery.•Umbilical cord blood cells (UCBCs) are effective carriers of therapeutic genes.•Triple-gene therapy with intra-thecal delivery has been found to be effective in SCI.•Genetic modification of UCBCs with therapeutic genes promotes healing processes in SCI.
Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28529158</pmid><doi>10.1016/j.brainresbull.2017.05.005</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Brain research bulletin, 2017-06, Vol.132, p.44-52 |
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| subjects | Adeno-virus Adenoviridae - genetics Angiogenin Animals CD56 Antigen - genetics CD56 Antigen - metabolism Cord Blood Stem Cell Transplantation Disease Models, Animal Escherichia coli Female Fetal Blood - cytology Genetic Therapy - methods Genetic Vectors Glial Cell Line-Derived Neurotrophic Factor - genetics Glial Cell Line-Derived Neurotrophic Factor - metabolism Glial cell-derived neurotrophic factor Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism HEK293 Cells Human umbilical cord blood mononuclear cell Humans Injections, Spinal Neural cell adhesion molecule Rats, Wistar Ribonuclease, Pancreatic - genetics Ribonuclease, Pancreatic - metabolism Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Spinal Cord Injuries - therapy Spinal cord injury Spinal Cord Regeneration - physiology Transduction, Genetic Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism Vector |
| title | Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats |
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