Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury
Abstract Background context Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous s...
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| Veröffentlicht in: | The spine journal 2012-11, Vol.12 (11), p.1040-1044 |
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| creator | Cheng, Ivan, MD Mayle, Robert E., MD Cox, Christopher A., MD Park, Don Y., MD Smith, Robert L., PhD Corcoran-Schwartz, Ian, BS Ponnusamy, Karthikeyan E., MD Oshtory, Rayshad, MD Smuck, Matthew W., MD Mitra, Raj, MD Kharazi, Alexander I., PhD Carragee, Eugene J., MD |
| description | Abstract Background context Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. Purpose We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Study design/setting Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Methods Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Results Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Conclusions Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques. |
| doi_str_mv | 10.1016/j.spinee.2012.09.005 |
| format | Article |
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The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. Purpose We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Study design/setting Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Methods Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Results Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Conclusions Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.</description><identifier>ISSN: 1529-9430</identifier><identifier>EISSN: 1878-1632</identifier><identifier>DOI: 10.1016/j.spinee.2012.09.005</identifier><identifier>PMID: 23063425</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Brain - cytology ; Brain - embryology ; Disease Models, Animal ; Female ; Fetus - cytology ; Functional recovery ; Gestational Age ; Humans ; Injections, Epidural ; Injections, Spinal ; Laminectomy ; Lumbar puncture ; Neural stem cells ; Neural Stem Cells - physiology ; Neural Stem Cells - transplantation ; Orthopedics ; Rats ; Rats, Long-Evans ; Recovery of Function ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology ; Spinal Cord Injuries - surgery ; Spinal cord injury ; Stem Cell Transplantation ; Treatment Outcome</subject><ispartof>The spine journal, 2012-11, Vol.12 (11), p.1040-1044</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-1f92fd1fdfbd26254b8f8d98144b75ca59166054ec4c3d98c223028f21d78c53</citedby><cites>FETCH-LOGICAL-c483t-1f92fd1fdfbd26254b8f8d98144b75ca59166054ec4c3d98c223028f21d78c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.spinee.2012.09.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23063425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Ivan, MD</creatorcontrib><creatorcontrib>Mayle, Robert E., MD</creatorcontrib><creatorcontrib>Cox, Christopher A., MD</creatorcontrib><creatorcontrib>Park, Don Y., MD</creatorcontrib><creatorcontrib>Smith, Robert L., PhD</creatorcontrib><creatorcontrib>Corcoran-Schwartz, Ian, BS</creatorcontrib><creatorcontrib>Ponnusamy, Karthikeyan E., MD</creatorcontrib><creatorcontrib>Oshtory, Rayshad, MD</creatorcontrib><creatorcontrib>Smuck, Matthew W., MD</creatorcontrib><creatorcontrib>Mitra, Raj, MD</creatorcontrib><creatorcontrib>Kharazi, Alexander I., PhD</creatorcontrib><creatorcontrib>Carragee, Eugene J., MD</creatorcontrib><title>Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury</title><title>The spine journal</title><addtitle>Spine J</addtitle><description>Abstract Background context Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. Purpose We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Study design/setting Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Methods Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Results Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Conclusions Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.</description><subject>Animals</subject><subject>Brain - cytology</subject><subject>Brain - embryology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fetus - cytology</subject><subject>Functional recovery</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Injections, Epidural</subject><subject>Injections, Spinal</subject><subject>Laminectomy</subject><subject>Lumbar puncture</subject><subject>Neural stem cells</subject><subject>Neural Stem Cells - physiology</subject><subject>Neural Stem Cells - transplantation</subject><subject>Orthopedics</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Recovery of Function</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal Cord Injuries - surgery</subject><subject>Spinal cord injury</subject><subject>Stem Cell Transplantation</subject><subject>Treatment Outcome</subject><issn>1529-9430</issn><issn>1878-1632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUcFu1DAQjRCoLaV_gJCPvSTYjp11LkioogWpEgd6t7z2WHVInMXjgPbvsbWlh16QDx7NvPdm5k3TvGe0Y5QNH6cODyECdJwy3tGxo1S-ai6Y2qmWDT1_XWLJx3YUPT1v3iJOlFK1Y_ysOec9HXrB5UXz53aLNoc1mpkYREBcIGayepIfgRi7ZSDzams1OuIC5hLmZCIeZhOzqdSKftwWE0mELZU6ZliIhXlGYnyGROqkJW_X5EiI05aO75o33swIV0__ZfNw--Xh5mt7__3u283n-9YK1eeW-ZF7x7zze8cHLsVeeeVGxYTY76Q1cmTDQKUAK2xf8paX1bjynLmdsrK_bK5Psoe0_toAs14C1slMhHVDzThnSo6SqQIVJ6hNK2ICrw8pLCYdNaO6Oq4nfXJcV8c1HXVxvNA-PHXY9gu4Z9I_iwvg0wkAZc3fAZJGGyBacCGBzdqt4X8dXgrYOcRQbvITjoDTuqVibtlFY-HoH_Xq9eisiJSn-r9Nl6pl</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Cheng, Ivan, MD</creator><creator>Mayle, Robert E., MD</creator><creator>Cox, Christopher A., MD</creator><creator>Park, Don Y., MD</creator><creator>Smith, Robert L., PhD</creator><creator>Corcoran-Schwartz, Ian, BS</creator><creator>Ponnusamy, Karthikeyan E., MD</creator><creator>Oshtory, Rayshad, MD</creator><creator>Smuck, Matthew W., MD</creator><creator>Mitra, Raj, MD</creator><creator>Kharazi, Alexander I., PhD</creator><creator>Carragee, Eugene J., MD</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>201211</creationdate><title>Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury</title><author>Cheng, Ivan, MD ; Mayle, Robert E., MD ; Cox, Christopher A., MD ; Park, Don Y., MD ; Smith, Robert L., PhD ; Corcoran-Schwartz, Ian, BS ; Ponnusamy, Karthikeyan E., MD ; Oshtory, Rayshad, MD ; Smuck, Matthew W., MD ; Mitra, Raj, MD ; Kharazi, Alexander I., PhD ; Carragee, Eugene J., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-1f92fd1fdfbd26254b8f8d98144b75ca59166054ec4c3d98c223028f21d78c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Brain - cytology</topic><topic>Brain - embryology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fetus - cytology</topic><topic>Functional recovery</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Injections, Epidural</topic><topic>Injections, Spinal</topic><topic>Laminectomy</topic><topic>Lumbar puncture</topic><topic>Neural stem cells</topic><topic>Neural Stem Cells - physiology</topic><topic>Neural Stem Cells - transplantation</topic><topic>Orthopedics</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Recovery of Function</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal Cord Injuries - surgery</topic><topic>Spinal cord injury</topic><topic>Stem Cell Transplantation</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Ivan, MD</creatorcontrib><creatorcontrib>Mayle, Robert E., MD</creatorcontrib><creatorcontrib>Cox, Christopher A., MD</creatorcontrib><creatorcontrib>Park, Don Y., MD</creatorcontrib><creatorcontrib>Smith, Robert L., PhD</creatorcontrib><creatorcontrib>Corcoran-Schwartz, Ian, BS</creatorcontrib><creatorcontrib>Ponnusamy, Karthikeyan E., MD</creatorcontrib><creatorcontrib>Oshtory, Rayshad, MD</creatorcontrib><creatorcontrib>Smuck, Matthew W., MD</creatorcontrib><creatorcontrib>Mitra, Raj, MD</creatorcontrib><creatorcontrib>Kharazi, Alexander I., PhD</creatorcontrib><creatorcontrib>Carragee, Eugene J., MD</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>The spine journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Ivan, MD</au><au>Mayle, Robert E., MD</au><au>Cox, Christopher A., MD</au><au>Park, Don Y., MD</au><au>Smith, Robert L., PhD</au><au>Corcoran-Schwartz, Ian, BS</au><au>Ponnusamy, Karthikeyan E., MD</au><au>Oshtory, Rayshad, MD</au><au>Smuck, Matthew W., MD</au><au>Mitra, Raj, MD</au><au>Kharazi, Alexander I., PhD</au><au>Carragee, Eugene J., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury</atitle><jtitle>The spine journal</jtitle><addtitle>Spine J</addtitle><date>2012-11</date><risdate>2012</risdate><volume>12</volume><issue>11</issue><spage>1040</spage><epage>1044</epage><pages>1040-1044</pages><issn>1529-9430</issn><eissn>1878-1632</eissn><abstract>Abstract Background context Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. Purpose We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Study design/setting Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Methods Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Results Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Conclusions Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23063425</pmid><doi>10.1016/j.spinee.2012.09.005</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Brain - cytology Brain - embryology Disease Models, Animal Female Fetus - cytology Functional recovery Gestational Age Humans Injections, Epidural Injections, Spinal Laminectomy Lumbar puncture Neural stem cells Neural Stem Cells - physiology Neural Stem Cells - transplantation Orthopedics Rats Rats, Long-Evans Recovery of Function Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Spinal Cord Injuries - surgery Spinal cord injury Stem Cell Transplantation Treatment Outcome |
| title | Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury |
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