Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair
Olfactory ensheathing cell (OEC) transplantation has emerged as a very promising therapy for spinal cord repair. In this study, we tested the ability of genetically modified OECs to secrete high levels of glial cell line‐derived neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene...
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| Veröffentlicht in: | Brain (London, England : 1878) England : 1878), 2004-03, Vol.127 (3), p.535-549 |
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| container_title | Brain (London, England : 1878) |
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| creator | Cao, Li Liu, Li Chen, Zhe‐Yu Wang, Li‐Mei Ye, Jun‐Li Qiu, Hai‐Yan Lu, Chang‐Lin He, Cheng |
| description | Olfactory ensheathing cell (OEC) transplantation has emerged as a very promising therapy for spinal cord repair. In this study, we tested the ability of genetically modified OECs to secrete high levels of glial cell line‐derived neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene was transduced into OECs using a retroviral‐based system. The engineered OECs were first characterized by their ability to express and secrete biologically active GDNF in vitro. After implantation into the spinal cord of adult rats with complete spinal cord transection, OEC survival and GDNF production were examined. The locomotor functions of animals were assessed and axon regeneration was evaluated at the morphological level. To our knowledge, we report for the first time that the genetically modified OECs are capable of producing GDNF in vivo to significantly improve recovery after spinal cord injury (SCI). This work combined the outgrowth‐promoting property of OECs with the neuroprotective effects of the additionally overexpressed neurotrophic factors and opens new avenues for the treatment of SCI. |
| doi_str_mv | 10.1093/brain/awh072 |
| format | Article |
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In this study, we tested the ability of genetically modified OECs to secrete high levels of glial cell line‐derived neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene was transduced into OECs using a retroviral‐based system. The engineered OECs were first characterized by their ability to express and secrete biologically active GDNF in vitro. After implantation into the spinal cord of adult rats with complete spinal cord transection, OEC survival and GDNF production were examined. The locomotor functions of animals were assessed and axon regeneration was evaluated at the morphological level. To our knowledge, we report for the first time that the genetically modified OECs are capable of producing GDNF in vivo to significantly improve recovery after spinal cord injury (SCI). This work combined the outgrowth‐promoting property of OECs with the neuroprotective effects of the additionally overexpressed neurotrophic factors and opens new avenues for the treatment of SCI.</description><identifier>ISSN: 0006-8950</identifier><identifier>ISSN: 1460-2156</identifier><identifier>EISSN: 1460-2156</identifier><identifier>DOI: 10.1093/brain/awh072</identifier><identifier>PMID: 14691064</identifier><identifier>CODEN: BRAIAK</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Axons - physiology ; Biological and medical sciences ; Cell Culture Techniques - methods ; Cell Separation - methods ; Cell Transplantation - methods ; CM = conditioned medium ; CSN = corticospinal neuron ; CST = corticospinal tract ; DMEM = Dulbecco’s modified Eagle medium ; Female ; GDNF = glial cell line‐derived neurotrophic factor ; Gene Expression ; gene therapy ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; GFAP = glial fibrillary acidic protein ; GFP = green fluorescent protein ; Glial Cell Line-Derived Neurotrophic Factor ; HRP = horseradish peroxidase ; Immunohistochemistry - methods ; LTR = long terminal repeat ; Medical sciences ; Myelin Sheath - secretion ; Myelin Sheath - transplantation ; Nerve Growth Factors - genetics ; Nerve Growth Factors - secretion ; Nerve Regeneration ; Neurology ; NF = neurofilament ; OECs = olfactory ensheathing cells ; Olfactory Bulb - cytology ; olfactory ensheathing cell ; PBS = phosphate‐buffered saline ; Rats ; Rats, Sprague-Dawley ; Retroviridae - genetics ; RSN = rubrospinal neuron ; SCI = spinal cord injury ; Spinal Cord Injuries - therapy ; spinal cord injury ; Transduction, Genetic - methods ; transplantation</subject><ispartof>Brain (London, England : 1878), 2004-03, Vol.127 (3), p.535-549</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Mar 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-55c8ebb4e8b0ad13bf299c47c31210af38ea6225fd97ca09d832b6ebe999f4553</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15576364$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14691064$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Li</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Chen, Zhe‐Yu</creatorcontrib><creatorcontrib>Wang, Li‐Mei</creatorcontrib><creatorcontrib>Ye, Jun‐Li</creatorcontrib><creatorcontrib>Qiu, Hai‐Yan</creatorcontrib><creatorcontrib>Lu, Chang‐Lin</creatorcontrib><creatorcontrib>He, Cheng</creatorcontrib><title>Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair</title><title>Brain (London, England : 1878)</title><addtitle>Brain</addtitle><description>Olfactory ensheathing cell (OEC) transplantation has emerged as a very promising therapy for spinal cord repair. In this study, we tested the ability of genetically modified OECs to secrete high levels of glial cell line‐derived neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene was transduced into OECs using a retroviral‐based system. The engineered OECs were first characterized by their ability to express and secrete biologically active GDNF in vitro. After implantation into the spinal cord of adult rats with complete spinal cord transection, OEC survival and GDNF production were examined. The locomotor functions of animals were assessed and axon regeneration was evaluated at the morphological level. To our knowledge, we report for the first time that the genetically modified OECs are capable of producing GDNF in vivo to significantly improve recovery after spinal cord injury (SCI). This work combined the outgrowth‐promoting property of OECs with the neuroprotective effects of the additionally overexpressed neurotrophic factors and opens new avenues for the treatment of SCI.</description><subject>Animals</subject><subject>Axons - physiology</subject><subject>Biological and medical sciences</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell Separation - methods</subject><subject>Cell Transplantation - methods</subject><subject>CM = conditioned medium</subject><subject>CSN = corticospinal neuron</subject><subject>CST = corticospinal tract</subject><subject>DMEM = Dulbecco’s modified Eagle medium</subject><subject>Female</subject><subject>GDNF = glial cell line‐derived neurotrophic factor</subject><subject>Gene Expression</subject><subject>gene therapy</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>GFAP = glial fibrillary acidic protein</subject><subject>GFP = green fluorescent protein</subject><subject>Glial Cell Line-Derived Neurotrophic Factor</subject><subject>HRP = horseradish peroxidase</subject><subject>Immunohistochemistry - methods</subject><subject>LTR = long terminal repeat</subject><subject>Medical sciences</subject><subject>Myelin Sheath - secretion</subject><subject>Myelin Sheath - transplantation</subject><subject>Nerve Growth Factors - genetics</subject><subject>Nerve Growth Factors - secretion</subject><subject>Nerve Regeneration</subject><subject>Neurology</subject><subject>NF = neurofilament</subject><subject>OECs = olfactory ensheathing cells</subject><subject>Olfactory Bulb - cytology</subject><subject>olfactory ensheathing cell</subject><subject>PBS = phosphate‐buffered saline</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retroviridae - genetics</subject><subject>RSN = rubrospinal neuron</subject><subject>SCI = spinal cord injury</subject><subject>Spinal Cord Injuries - therapy</subject><subject>spinal cord injury</subject><subject>Transduction, Genetic - methods</subject><subject>transplantation</subject><issn>0006-8950</issn><issn>1460-2156</issn><issn>1460-2156</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c1rFDEYBvAgFrtWb55lEJQeOjbfH0ettisu9qJFPBgymXe6qTOTNZlF979vtrtY8KCn8JIfD8n7IPSM4NcEG3baJBfGU_driRV9gGaES1xTIuRDNMMYy1obgQ_R45xvMCacUfkIHRZkCJZ8hr5f9p3zU0ybCsa8BDctw3hdeej7XF3DCFPwru831RDb0AVoqylWGXyCCaqLd5_Ot_MqxSGWOa_C6PrKx9RWCVYupCfooHN9hqf78wh9OX__-WxeLy4vPpy9WdReEDrVQngNTcNBN9i1hDUdNcZz5RmhBLuOaXCSUtG1RnmHTasZbSQ0YIzpuBDsCL3a5Zan_FxDnuwQ8vYTboS4zlYRabAwpsDjf0KildBcSK3-m0mUVIIRWeCLv-BNXKeyiWKM4FQLygs62SGfYs4JOrtKYXBpYwm22yLtXZF2V2Thz_eZ62aA9h7vmyvg5R64XBrqkht9yPdOCCXZnat3LuQJfv-5d-mHlYopYedfv9mPb-dXV1xyu2C36_e2dg</recordid><startdate>20040301</startdate><enddate>20040301</enddate><creator>Cao, Li</creator><creator>Liu, Li</creator><creator>Chen, Zhe‐Yu</creator><creator>Wang, Li‐Mei</creator><creator>Ye, Jun‐Li</creator><creator>Qiu, Hai‐Yan</creator><creator>Lu, Chang‐Lin</creator><creator>He, Cheng</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7QO</scope><scope>7X8</scope></search><sort><creationdate>20040301</creationdate><title>Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair</title><author>Cao, Li ; Liu, Li ; Chen, Zhe‐Yu ; Wang, Li‐Mei ; Ye, Jun‐Li ; Qiu, Hai‐Yan ; Lu, Chang‐Lin ; He, Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-55c8ebb4e8b0ad13bf299c47c31210af38ea6225fd97ca09d832b6ebe999f4553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Axons - physiology</topic><topic>Biological and medical sciences</topic><topic>Cell Culture Techniques - methods</topic><topic>Cell Separation - methods</topic><topic>Cell Transplantation - methods</topic><topic>CM = conditioned medium</topic><topic>CSN = corticospinal neuron</topic><topic>CST = corticospinal tract</topic><topic>DMEM = Dulbecco’s modified Eagle medium</topic><topic>Female</topic><topic>GDNF = glial cell line‐derived neurotrophic factor</topic><topic>Gene Expression</topic><topic>gene therapy</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - administration & dosage</topic><topic>GFAP = glial fibrillary acidic protein</topic><topic>GFP = green fluorescent protein</topic><topic>Glial Cell Line-Derived Neurotrophic Factor</topic><topic>HRP = horseradish peroxidase</topic><topic>Immunohistochemistry - methods</topic><topic>LTR = long terminal repeat</topic><topic>Medical sciences</topic><topic>Myelin Sheath - secretion</topic><topic>Myelin Sheath - transplantation</topic><topic>Nerve Growth Factors - genetics</topic><topic>Nerve Growth Factors - secretion</topic><topic>Nerve Regeneration</topic><topic>Neurology</topic><topic>NF = neurofilament</topic><topic>OECs = olfactory ensheathing cells</topic><topic>Olfactory Bulb - cytology</topic><topic>olfactory ensheathing cell</topic><topic>PBS = phosphate‐buffered saline</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retroviridae - genetics</topic><topic>RSN = rubrospinal neuron</topic><topic>SCI = spinal cord injury</topic><topic>Spinal Cord Injuries - therapy</topic><topic>spinal cord injury</topic><topic>Transduction, Genetic - methods</topic><topic>transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Li</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Chen, Zhe‐Yu</creatorcontrib><creatorcontrib>Wang, Li‐Mei</creatorcontrib><creatorcontrib>Ye, Jun‐Li</creatorcontrib><creatorcontrib>Qiu, Hai‐Yan</creatorcontrib><creatorcontrib>Lu, Chang‐Lin</creatorcontrib><creatorcontrib>He, Cheng</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain (London, England : 1878)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Li</au><au>Liu, Li</au><au>Chen, Zhe‐Yu</au><au>Wang, Li‐Mei</au><au>Ye, Jun‐Li</au><au>Qiu, Hai‐Yan</au><au>Lu, Chang‐Lin</au><au>He, Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair</atitle><jtitle>Brain (London, England : 1878)</jtitle><addtitle>Brain</addtitle><date>2004-03-01</date><risdate>2004</risdate><volume>127</volume><issue>3</issue><spage>535</spage><epage>549</epage><pages>535-549</pages><issn>0006-8950</issn><issn>1460-2156</issn><eissn>1460-2156</eissn><coden>BRAIAK</coden><abstract>Olfactory ensheathing cell (OEC) transplantation has emerged as a very promising therapy for spinal cord repair. In this study, we tested the ability of genetically modified OECs to secrete high levels of glial cell line‐derived neurotrophic factor (GDNF) to promote spinal cord repair. The GDNF gene was transduced into OECs using a retroviral‐based system. The engineered OECs were first characterized by their ability to express and secrete biologically active GDNF in vitro. After implantation into the spinal cord of adult rats with complete spinal cord transection, OEC survival and GDNF production were examined. The locomotor functions of animals were assessed and axon regeneration was evaluated at the morphological level. To our knowledge, we report for the first time that the genetically modified OECs are capable of producing GDNF in vivo to significantly improve recovery after spinal cord injury (SCI). This work combined the outgrowth‐promoting property of OECs with the neuroprotective effects of the additionally overexpressed neurotrophic factors and opens new avenues for the treatment of SCI.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>14691064</pmid><doi>10.1093/brain/awh072</doi><tpages>15</tpages></addata></record> |
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| ispartof | Brain (London, England : 1878), 2004-03, Vol.127 (3), p.535-549 |
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| subjects | Animals Axons - physiology Biological and medical sciences Cell Culture Techniques - methods Cell Separation - methods Cell Transplantation - methods CM = conditioned medium CSN = corticospinal neuron CST = corticospinal tract DMEM = Dulbecco’s modified Eagle medium Female GDNF = glial cell line‐derived neurotrophic factor Gene Expression gene therapy Genetic Therapy - methods Genetic Vectors - administration & dosage GFAP = glial fibrillary acidic protein GFP = green fluorescent protein Glial Cell Line-Derived Neurotrophic Factor HRP = horseradish peroxidase Immunohistochemistry - methods LTR = long terminal repeat Medical sciences Myelin Sheath - secretion Myelin Sheath - transplantation Nerve Growth Factors - genetics Nerve Growth Factors - secretion Nerve Regeneration Neurology NF = neurofilament OECs = olfactory ensheathing cells Olfactory Bulb - cytology olfactory ensheathing cell PBS = phosphate‐buffered saline Rats Rats, Sprague-Dawley Retroviridae - genetics RSN = rubrospinal neuron SCI = spinal cord injury Spinal Cord Injuries - therapy spinal cord injury Transduction, Genetic - methods transplantation |
| title | Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair |
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