Safety of Epicenter Versus Intact Parenchyma as a Transplantation Site for Human Neural Stem Cells for Spinal Cord Injury Therapy
This study compared transplantation into the spinal cord injury (SCI) epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats and assessed the survival, differentiation, and migration of human central nervous system‐derived neural stem cells (hCNS‐SCns)....
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| description | This study compared transplantation into the spinal cord injury (SCI) epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats and assessed the survival, differentiation, and migration of human central nervous system‐derived neural stem cells (hCNS‐SCns). Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Findings suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI.
Neural stem cell transplantation may have the potential to yield repair and recovery of function in central nervous system injury and disease, including spinal cord injury (SCI). Multiple pathological processes are initiated at the epicenter of a traumatic spinal cord injury; these are generally thought to make the epicenter a particularly hostile microenvironment. Conversely, the injury epicenter is an appealing potential site of therapeutic human central nervous system‐derived neural stem cell (hCNS‐SCns) transplantation because of both its surgical accessibility and the avoidance of spared spinal cord tissue. In this study, we compared hCNS‐SCns transplantation into the SCI epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats, and assessed the cell survival, differentiation, and migration. Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Migration and fate profile were unaffected by transplantation site. However, although transplantation site did not alter the proportion of human astrocytes, EPI transplantation shifted the localization of these cells and exhibited a correlation with calcitonin gene‐related peptide fiber sprouting. Critically, no changes in mechanical allodynia or thermal hyperalgesia were observed. Taken together, these data suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI. |
| doi_str_mv | 10.5966/sctm.2012-0110 |
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Neural stem cell transplantation may have the potential to yield repair and recovery of function in central nervous system injury and disease, including spinal cord injury (SCI). Multiple pathological processes are initiated at the epicenter of a traumatic spinal cord injury; these are generally thought to make the epicenter a particularly hostile microenvironment. Conversely, the injury epicenter is an appealing potential site of therapeutic human central nervous system‐derived neural stem cell (hCNS‐SCns) transplantation because of both its surgical accessibility and the avoidance of spared spinal cord tissue. In this study, we compared hCNS‐SCns transplantation into the SCI epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats, and assessed the cell survival, differentiation, and migration. Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Migration and fate profile were unaffected by transplantation site. However, although transplantation site did not alter the proportion of human astrocytes, EPI transplantation shifted the localization of these cells and exhibited a correlation with calcitonin gene‐related peptide fiber sprouting. Critically, no changes in mechanical allodynia or thermal hyperalgesia were observed. Taken together, these data suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI.</description><identifier>ISSN: 2157-6564</identifier><identifier>EISSN: 2157-6580</identifier><identifier>DOI: 10.5966/sctm.2012-0110</identifier><identifier>PMID: 23413374</identifier><language>eng</language><publisher>United States: AlphaMed Press</publisher><subject>Animals ; Astrocytes - metabolism ; Astrocytes - pathology ; Behavior, Animal ; Biomarkers - metabolism ; Calcitonin Gene-Related Peptide - metabolism ; Cell Movement ; Cell Proliferation ; Cell Survival ; Central nervous system ; CGRP ; Contusions ; Data analysis ; Disease Models, Animal ; Fate ; Female ; Humans ; Hyperalgesia ; Hyperalgesia - etiology ; Hyperalgesia - physiopathology ; Hyperalgesia - psychology ; Lymphocytes ; Mechanical allodynia ; Migration ; Neural stem cells ; Neural Stem Cells - metabolism ; Neural Stem Cells - transplantation ; Neurogenesis ; Neurons - metabolism ; Neurons - pathology ; Neurons - transplantation ; Pain ; Pain Threshold ; Parenchyma ; Rats ; Rats, Nude ; Spheroids, Cellular ; Spinal cord injuries ; Spinal Cord Injuries - metabolism ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology ; Spinal Cord Injuries - psychology ; Spinal Cord Injuries - surgery ; Spinal cord injury ; Stem Cell Niche ; Stem cell transplantation ; Stem Cell Transplantation - adverse effects ; Stem Cell Transplantation - methods ; Stem cells ; Studies ; Thermal hyperalgesia ; Time Factors ; Tissue-Specific Progenitor and Stem Cells ; Transplants & implants</subject><ispartof>Stem cells translational medicine, 2013-03, Vol.2 (3), p.204-216</ispartof><rights>2013 AlphaMed Press</rights><rights>2013. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). 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Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Findings suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI.
Neural stem cell transplantation may have the potential to yield repair and recovery of function in central nervous system injury and disease, including spinal cord injury (SCI). Multiple pathological processes are initiated at the epicenter of a traumatic spinal cord injury; these are generally thought to make the epicenter a particularly hostile microenvironment. Conversely, the injury epicenter is an appealing potential site of therapeutic human central nervous system‐derived neural stem cell (hCNS‐SCns) transplantation because of both its surgical accessibility and the avoidance of spared spinal cord tissue. In this study, we compared hCNS‐SCns transplantation into the SCI epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats, and assessed the cell survival, differentiation, and migration. Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Migration and fate profile were unaffected by transplantation site. However, although transplantation site did not alter the proportion of human astrocytes, EPI transplantation shifted the localization of these cells and exhibited a correlation with calcitonin gene‐related peptide fiber sprouting. Critically, no changes in mechanical allodynia or thermal hyperalgesia were observed. Taken together, these data suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI.</description><subject>Animals</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Behavior, Animal</subject><subject>Biomarkers - metabolism</subject><subject>Calcitonin Gene-Related Peptide - metabolism</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Central nervous system</subject><subject>CGRP</subject><subject>Contusions</subject><subject>Data analysis</subject><subject>Disease Models, Animal</subject><subject>Fate</subject><subject>Female</subject><subject>Humans</subject><subject>Hyperalgesia</subject><subject>Hyperalgesia - etiology</subject><subject>Hyperalgesia - physiopathology</subject><subject>Hyperalgesia - psychology</subject><subject>Lymphocytes</subject><subject>Mechanical allodynia</subject><subject>Migration</subject><subject>Neural stem cells</subject><subject>Neural Stem Cells - metabolism</subject><subject>Neural Stem Cells - transplantation</subject><subject>Neurogenesis</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neurons - transplantation</subject><subject>Pain</subject><subject>Pain Threshold</subject><subject>Parenchyma</subject><subject>Rats</subject><subject>Rats, Nude</subject><subject>Spheroids, Cellular</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal Cord Injuries - psychology</subject><subject>Spinal Cord Injuries - surgery</subject><subject>Spinal cord injury</subject><subject>Stem Cell Niche</subject><subject>Stem cell transplantation</subject><subject>Stem Cell Transplantation - adverse effects</subject><subject>Stem Cell Transplantation - methods</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Thermal hyperalgesia</subject><subject>Time Factors</subject><subject>Tissue-Specific Progenitor and Stem Cells</subject><subject>Transplants & implants</subject><issn>2157-6564</issn><issn>2157-6580</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFUUtv1DAYtBAVrdpeOSJLXLhk8StOckFCUaGVKqiUhavl9X5mvUriYCdFOfLP63TLCrjUB79mPJrxIPSaklVeSfk-mrFbMUJZRiglL9AZo3mRybwkL497KU7RZYx7koasZMXIK3TKuKCcF-IM_W60hXHG3uKrwRnoRwj4O4Q4RXzTj9qM-E4H6M1u7jTWEWu8DrqPQ6sTOjrf48aNgK0P-HrqdI-_wBR0i5sROlxD28ZHrBlcn25rH7ZJdz-FGa93EPQwX6ATq9sIl0_rOfr26WpdX2e3Xz_f1B9vMyNkKbLCyAoKWoqSQc6k4Jstr7i0xJIit6IELnLDoOBgCr6RlhKab6im1gpSmW3Bz9GHg-4wbTrYLlGTTzUE1-kwK6-d-hfp3U798PeKy7wqZJ4E3j0JBP9zgjiqzkWTEuoe_BQV5VTyMjlkifr2P-reTyF9QFSMVYSWTPJFcHVgmeBjDGCPZihRS8FqKVgtBaul4PTgzd8RjvQ_dSZCdSD8ci3Mz8ippl7zdOIszYI_AGeAs2o</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Piltti, Katja M.</creator><creator>Salazar, Desirée L.</creator><creator>Uchida, Nobuko</creator><creator>Cummings, Brian J.</creator><creator>Anderson, Aileen J.</creator><general>AlphaMed Press</general><general>Oxford University Press</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>3V.</scope><scope>7X7</scope><scope>7XB</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>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201303</creationdate><title>Safety of Epicenter Versus Intact Parenchyma as a Transplantation Site for Human Neural Stem Cells for Spinal Cord Injury Therapy</title><author>Piltti, Katja M. ; Salazar, Desirée L. ; Uchida, Nobuko ; Cummings, Brian J. ; Anderson, Aileen J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4684-7c69e718482e52643bd3936f0f075f48e345c2e73ec73b6f1015b1a1ff409cd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - pathology</topic><topic>Behavior, Animal</topic><topic>Biomarkers - metabolism</topic><topic>Calcitonin Gene-Related Peptide - metabolism</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Central nervous system</topic><topic>CGRP</topic><topic>Contusions</topic><topic>Data analysis</topic><topic>Disease Models, Animal</topic><topic>Fate</topic><topic>Female</topic><topic>Humans</topic><topic>Hyperalgesia</topic><topic>Hyperalgesia - etiology</topic><topic>Hyperalgesia - physiopathology</topic><topic>Hyperalgesia - psychology</topic><topic>Lymphocytes</topic><topic>Mechanical allodynia</topic><topic>Migration</topic><topic>Neural stem cells</topic><topic>Neural Stem Cells - metabolism</topic><topic>Neural Stem Cells - transplantation</topic><topic>Neurogenesis</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neurons - transplantation</topic><topic>Pain</topic><topic>Pain Threshold</topic><topic>Parenchyma</topic><topic>Rats</topic><topic>Rats, Nude</topic><topic>Spheroids, Cellular</topic><topic>Spinal cord injuries</topic><topic>Spinal Cord Injuries - metabolism</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal Cord Injuries - psychology</topic><topic>Spinal Cord Injuries - surgery</topic><topic>Spinal cord injury</topic><topic>Stem Cell Niche</topic><topic>Stem cell transplantation</topic><topic>Stem Cell Transplantation - adverse effects</topic><topic>Stem Cell Transplantation - methods</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Thermal hyperalgesia</topic><topic>Time Factors</topic><topic>Tissue-Specific Progenitor and Stem Cells</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piltti, Katja M.</creatorcontrib><creatorcontrib>Salazar, Desirée L.</creatorcontrib><creatorcontrib>Uchida, Nobuko</creatorcontrib><creatorcontrib>Cummings, Brian J.</creatorcontrib><creatorcontrib>Anderson, Aileen J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cells translational medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Piltti, Katja M.</au><au>Salazar, Desirée L.</au><au>Uchida, Nobuko</au><au>Cummings, Brian J.</au><au>Anderson, Aileen J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety of Epicenter Versus Intact Parenchyma as a Transplantation Site for Human Neural Stem Cells for Spinal Cord Injury Therapy</atitle><jtitle>Stem cells translational medicine</jtitle><addtitle>Stem Cells Transl Med</addtitle><date>2013-03</date><risdate>2013</risdate><volume>2</volume><issue>3</issue><spage>204</spage><epage>216</epage><pages>204-216</pages><issn>2157-6564</issn><eissn>2157-6580</eissn><abstract>This study compared transplantation into the spinal cord injury (SCI) epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats and assessed the survival, differentiation, and migration of human central nervous system‐derived neural stem cells (hCNS‐SCns). Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Findings suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI.
Neural stem cell transplantation may have the potential to yield repair and recovery of function in central nervous system injury and disease, including spinal cord injury (SCI). Multiple pathological processes are initiated at the epicenter of a traumatic spinal cord injury; these are generally thought to make the epicenter a particularly hostile microenvironment. Conversely, the injury epicenter is an appealing potential site of therapeutic human central nervous system‐derived neural stem cell (hCNS‐SCns) transplantation because of both its surgical accessibility and the avoidance of spared spinal cord tissue. In this study, we compared hCNS‐SCns transplantation into the SCI epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion‐injured athymic nude rats, and assessed the cell survival, differentiation, and migration. Regardless of transplantation site, hCNS‐SCns survived and proliferated; however, the total number of hCNS‐SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Migration and fate profile were unaffected by transplantation site. However, although transplantation site did not alter the proportion of human astrocytes, EPI transplantation shifted the localization of these cells and exhibited a correlation with calcitonin gene‐related peptide fiber sprouting. Critically, no changes in mechanical allodynia or thermal hyperalgesia were observed. Taken together, these data suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post‐SCI.</abstract><cop>United States</cop><pub>AlphaMed Press</pub><pmid>23413374</pmid><doi>10.5966/sctm.2012-0110</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Astrocytes - metabolism Astrocytes - pathology Behavior, Animal Biomarkers - metabolism Calcitonin Gene-Related Peptide - metabolism Cell Movement Cell Proliferation Cell Survival Central nervous system CGRP Contusions Data analysis Disease Models, Animal Fate Female Humans Hyperalgesia Hyperalgesia - etiology Hyperalgesia - physiopathology Hyperalgesia - psychology Lymphocytes Mechanical allodynia Migration Neural stem cells Neural Stem Cells - metabolism Neural Stem Cells - transplantation Neurogenesis Neurons - metabolism Neurons - pathology Neurons - transplantation Pain Pain Threshold Parenchyma Rats Rats, Nude Spheroids, Cellular Spinal cord injuries Spinal Cord Injuries - metabolism Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Spinal Cord Injuries - psychology Spinal Cord Injuries - surgery Spinal cord injury Stem Cell Niche Stem cell transplantation Stem Cell Transplantation - adverse effects Stem Cell Transplantation - methods Stem cells Studies Thermal hyperalgesia Time Factors Tissue-Specific Progenitor and Stem Cells Transplants & implants |
| title | Safety of Epicenter Versus Intact Parenchyma as a Transplantation Site for Human Neural Stem Cells for Spinal Cord Injury Therapy |
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