Therapeutic Benefit of Intrathecal Injection of Marrow Stromal Cells on Ischemia-Injured Spinal Cord
Background Prophylactic transplantation of marrow stromal cells (MSCs) before spinal cord ischemia has been shown to attenuate neurologic injures. We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord. Methods Marrow stromal cells were expanded in vitro and prelabel...
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creator | Shi, Enyi, MD, PhD Kazui, Teruhisa, MD, PhD Jiang, Xiaojing, MD Washiyama, Naoki, MD, PhD Yamashita, Katsushi, MD, PhD Terada, Hitoshi, MD, PhD Bashar, Abul Hasan Muhammad, MBBS, PhD |
description | Background Prophylactic transplantation of marrow stromal cells (MSCs) before spinal cord ischemia has been shown to attenuate neurologic injures. We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord. Methods Marrow stromal cells were expanded in vitro and prelabeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Four groups were enrolled. About 1 × 108 MSCs were intrathecally injected 2 hours (group MSC-2h), 24 hours (group MSC-24h), or 48 hours (group MSC-48h) after spinal cord ischemia, respectively. The control group received intrathecal injection of medium alone. Hind-limb motor function was assessed during a 28-day recovery period with Tarlov criteria, and then histologic examination was performed. Results Marrow stromal cells still could be found in the spinal cord 4 weeks after transplantation. The capillary density in the ventral gray matter was significantly increased in the three MSC-treated groups ( p < 0.01 versus control group, respectively). After a 28-day recovery, marked functional improvement was detected in group MSC-2h (from day 1 to 28, p < 0.05, versus control group, respectively) and group MSC-24h (from day 14 to 28, p < 0.05, versus control group, respectively), but not in group MSC-48h. The number of intact motor neurons was much greater in group MSC-2h ( p < 0.05, versus control group). Conclusions Intrathecal injection of MSCs enhances angiogenesis in the host spinal cord and improves the motor functional recovery after spinal cord ischemia. The therapeutic time window is critical for the therapeutic effect of MSCs. |
doi_str_mv | 10.1016/j.athoracsur.2006.11.048 |
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We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord. Methods Marrow stromal cells were expanded in vitro and prelabeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Four groups were enrolled. About 1 × 108 MSCs were intrathecally injected 2 hours (group MSC-2h), 24 hours (group MSC-24h), or 48 hours (group MSC-48h) after spinal cord ischemia, respectively. The control group received intrathecal injection of medium alone. Hind-limb motor function was assessed during a 28-day recovery period with Tarlov criteria, and then histologic examination was performed. Results Marrow stromal cells still could be found in the spinal cord 4 weeks after transplantation. The capillary density in the ventral gray matter was significantly increased in the three MSC-treated groups ( p < 0.01 versus control group, respectively). After a 28-day recovery, marked functional improvement was detected in group MSC-2h (from day 1 to 28, p < 0.05, versus control group, respectively) and group MSC-24h (from day 14 to 28, p < 0.05, versus control group, respectively), but not in group MSC-48h. The number of intact motor neurons was much greater in group MSC-2h ( p < 0.05, versus control group). Conclusions Intrathecal injection of MSCs enhances angiogenesis in the host spinal cord and improves the motor functional recovery after spinal cord ischemia. The therapeutic time window is critical for the therapeutic effect of MSCs.</description><identifier>ISSN: 0003-4975</identifier><identifier>EISSN: 1552-6259</identifier><identifier>DOI: 10.1016/j.athoracsur.2006.11.048</identifier><identifier>PMID: 17383362</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Biopsy, Needle ; Bone Marrow Transplantation - methods ; Cardiothoracic Surgery ; Disease Models, Animal ; Immunohistochemistry ; Injections, Spinal ; Neovascularization, Physiologic ; Neurologic Examination ; Rabbits ; Random Allocation ; Recovery of Function ; Reference Values ; Sensitivity and Specificity ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - therapy ; Spinal Cord Ischemia - pathology ; Spinal Cord Ischemia - therapy ; Stromal Cells - transplantation ; Surgery ; Transplantation, Autologous</subject><ispartof>The Annals of thoracic surgery, 2007-04, Vol.83 (4), p.1484-1490</ispartof><rights>The Society of Thoracic Surgeons</rights><rights>2007 The Society of Thoracic Surgeons</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-935704bb11accbc2d670d0bbe23c5533b7b244ee2cc1e7a9efec93221adf4a7e3</citedby><cites>FETCH-LOGICAL-c579t-935704bb11accbc2d670d0bbe23c5533b7b244ee2cc1e7a9efec93221adf4a7e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17383362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Enyi, MD, PhD</creatorcontrib><creatorcontrib>Kazui, Teruhisa, MD, PhD</creatorcontrib><creatorcontrib>Jiang, Xiaojing, MD</creatorcontrib><creatorcontrib>Washiyama, Naoki, MD, PhD</creatorcontrib><creatorcontrib>Yamashita, Katsushi, MD, PhD</creatorcontrib><creatorcontrib>Terada, Hitoshi, MD, PhD</creatorcontrib><creatorcontrib>Bashar, Abul Hasan Muhammad, MBBS, PhD</creatorcontrib><title>Therapeutic Benefit of Intrathecal Injection of Marrow Stromal Cells on Ischemia-Injured Spinal Cord</title><title>The Annals of thoracic surgery</title><addtitle>Ann Thorac Surg</addtitle><description>Background Prophylactic transplantation of marrow stromal cells (MSCs) before spinal cord ischemia has been shown to attenuate neurologic injures. We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord. Methods Marrow stromal cells were expanded in vitro and prelabeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Four groups were enrolled. About 1 × 108 MSCs were intrathecally injected 2 hours (group MSC-2h), 24 hours (group MSC-24h), or 48 hours (group MSC-48h) after spinal cord ischemia, respectively. The control group received intrathecal injection of medium alone. Hind-limb motor function was assessed during a 28-day recovery period with Tarlov criteria, and then histologic examination was performed. Results Marrow stromal cells still could be found in the spinal cord 4 weeks after transplantation. The capillary density in the ventral gray matter was significantly increased in the three MSC-treated groups ( p < 0.01 versus control group, respectively). After a 28-day recovery, marked functional improvement was detected in group MSC-2h (from day 1 to 28, p < 0.05, versus control group, respectively) and group MSC-24h (from day 14 to 28, p < 0.05, versus control group, respectively), but not in group MSC-48h. The number of intact motor neurons was much greater in group MSC-2h ( p < 0.05, versus control group). Conclusions Intrathecal injection of MSCs enhances angiogenesis in the host spinal cord and improves the motor functional recovery after spinal cord ischemia. The therapeutic time window is critical for the therapeutic effect of MSCs.</description><subject>Animals</subject><subject>Biopsy, Needle</subject><subject>Bone Marrow Transplantation - methods</subject><subject>Cardiothoracic Surgery</subject><subject>Disease Models, Animal</subject><subject>Immunohistochemistry</subject><subject>Injections, Spinal</subject><subject>Neovascularization, Physiologic</subject><subject>Neurologic Examination</subject><subject>Rabbits</subject><subject>Random Allocation</subject><subject>Recovery of Function</subject><subject>Reference Values</subject><subject>Sensitivity and Specificity</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - therapy</subject><subject>Spinal Cord Ischemia - pathology</subject><subject>Spinal Cord Ischemia - therapy</subject><subject>Stromal Cells - transplantation</subject><subject>Surgery</subject><subject>Transplantation, Autologous</subject><issn>0003-4975</issn><issn>1552-6259</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU-P0zAQxS0EYkvhK6CcuCU7tpO4uSCxFX8qLeLQ5Ww544nqkMTFTljtt8dRK63EiZNtvTfzxr9hLONQcOD1bV-Y-eSDwbiEQgDUBecFlLsXbMOrSuS1qJqXbAMAMi8bVd2wNzH26SmS_JrdcCV3UtZiw-zDiYI50zI7zO5oos7Nme-ywzSHlEFohnTvCWfnp1X4bkLwj9lxDn5M2p6GIWZJOkQ80ehMntxLIJsdz25aDT7Yt-xVZ4ZI767nlv388vlh_y2___H1sP90n2OlmjlvZKWgbFvODWKLwtYKLLQtCYlVJWWrWlGWRAKRkzINdYSNFIIb25VGkdyyD5e-5-B_LxRnPbqIaUIzkV-iViBByQRly3YXIwYfY6BOn4MbTXjSHPRKWPf6mbBeCWvOdSKcSt9fM5Z2JPtceEWaDHcXA6Wf_nEUdERHE5J1IWHU1rv_Sfn4TxMc3OTSNn7RE8XeLyHBjZrrKDTo47rpddFQgxBNWcu_SgmofQ</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Shi, Enyi, MD, PhD</creator><creator>Kazui, Teruhisa, MD, PhD</creator><creator>Jiang, Xiaojing, MD</creator><creator>Washiyama, Naoki, MD, PhD</creator><creator>Yamashita, Katsushi, MD, PhD</creator><creator>Terada, Hitoshi, MD, PhD</creator><creator>Bashar, Abul Hasan Muhammad, MBBS, PhD</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>20070401</creationdate><title>Therapeutic Benefit of Intrathecal Injection of Marrow Stromal Cells on Ischemia-Injured Spinal Cord</title><author>Shi, Enyi, MD, PhD ; Kazui, Teruhisa, MD, PhD ; Jiang, Xiaojing, MD ; Washiyama, Naoki, MD, PhD ; Yamashita, Katsushi, MD, PhD ; Terada, Hitoshi, MD, PhD ; Bashar, Abul Hasan Muhammad, MBBS, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c579t-935704bb11accbc2d670d0bbe23c5533b7b244ee2cc1e7a9efec93221adf4a7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Biopsy, Needle</topic><topic>Bone Marrow Transplantation - methods</topic><topic>Cardiothoracic Surgery</topic><topic>Disease Models, Animal</topic><topic>Immunohistochemistry</topic><topic>Injections, Spinal</topic><topic>Neovascularization, Physiologic</topic><topic>Neurologic Examination</topic><topic>Rabbits</topic><topic>Random Allocation</topic><topic>Recovery of Function</topic><topic>Reference Values</topic><topic>Sensitivity and Specificity</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - therapy</topic><topic>Spinal Cord Ischemia - pathology</topic><topic>Spinal Cord Ischemia - therapy</topic><topic>Stromal Cells - transplantation</topic><topic>Surgery</topic><topic>Transplantation, Autologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Enyi, MD, PhD</creatorcontrib><creatorcontrib>Kazui, Teruhisa, MD, PhD</creatorcontrib><creatorcontrib>Jiang, Xiaojing, MD</creatorcontrib><creatorcontrib>Washiyama, Naoki, MD, PhD</creatorcontrib><creatorcontrib>Yamashita, Katsushi, MD, PhD</creatorcontrib><creatorcontrib>Terada, Hitoshi, MD, PhD</creatorcontrib><creatorcontrib>Bashar, Abul Hasan Muhammad, MBBS, PhD</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 Annals of thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Enyi, MD, PhD</au><au>Kazui, Teruhisa, MD, PhD</au><au>Jiang, Xiaojing, MD</au><au>Washiyama, Naoki, MD, PhD</au><au>Yamashita, Katsushi, MD, PhD</au><au>Terada, Hitoshi, MD, PhD</au><au>Bashar, Abul Hasan Muhammad, MBBS, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic Benefit of Intrathecal Injection of Marrow Stromal Cells on Ischemia-Injured Spinal Cord</atitle><jtitle>The Annals of thoracic surgery</jtitle><addtitle>Ann Thorac Surg</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>83</volume><issue>4</issue><spage>1484</spage><epage>1490</epage><pages>1484-1490</pages><issn>0003-4975</issn><eissn>1552-6259</eissn><abstract>Background Prophylactic transplantation of marrow stromal cells (MSCs) before spinal cord ischemia has been shown to attenuate neurologic injures. We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord. Methods Marrow stromal cells were expanded in vitro and prelabeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Four groups were enrolled. About 1 × 108 MSCs were intrathecally injected 2 hours (group MSC-2h), 24 hours (group MSC-24h), or 48 hours (group MSC-48h) after spinal cord ischemia, respectively. The control group received intrathecal injection of medium alone. Hind-limb motor function was assessed during a 28-day recovery period with Tarlov criteria, and then histologic examination was performed. Results Marrow stromal cells still could be found in the spinal cord 4 weeks after transplantation. The capillary density in the ventral gray matter was significantly increased in the three MSC-treated groups ( p < 0.01 versus control group, respectively). After a 28-day recovery, marked functional improvement was detected in group MSC-2h (from day 1 to 28, p < 0.05, versus control group, respectively) and group MSC-24h (from day 14 to 28, p < 0.05, versus control group, respectively), but not in group MSC-48h. The number of intact motor neurons was much greater in group MSC-2h ( p < 0.05, versus control group). Conclusions Intrathecal injection of MSCs enhances angiogenesis in the host spinal cord and improves the motor functional recovery after spinal cord ischemia. The therapeutic time window is critical for the therapeutic effect of MSCs.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>17383362</pmid><doi>10.1016/j.athoracsur.2006.11.048</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biopsy, Needle Bone Marrow Transplantation - methods Cardiothoracic Surgery Disease Models, Animal Immunohistochemistry Injections, Spinal Neovascularization, Physiologic Neurologic Examination Rabbits Random Allocation Recovery of Function Reference Values Sensitivity and Specificity Spinal Cord Injuries - pathology Spinal Cord Injuries - therapy Spinal Cord Ischemia - pathology Spinal Cord Ischemia - therapy Stromal Cells - transplantation Surgery Transplantation, Autologous |
title | Therapeutic Benefit of Intrathecal Injection of Marrow Stromal Cells on Ischemia-Injured Spinal Cord |
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