Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma
OBJECTIVE:To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant changes...
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| Veröffentlicht in: | Critical care medicine 2011-11, Vol.39 (11), p.2501-2510 |
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| creator | Zanier, Elisa R Montinaro, Mery Vigano, Mariele Villa, Pia Fumagalli, Stefano Pischiutta, Francesca Longhi, Luca Leoni, Matteo L Rebulla, Paolo Stocchetti, Nino Lazzari, Lorenza De Simoni, Maria-Grazia |
| description | OBJECTIVE:To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant changes in the environment in which they are infused.
DESIGN:Prospective experimental study.
SETTING:Research laboratory.
SUBJECTS:Male C57Bl/6 mice.
INTERVENTIONS:Mice were subjected to controlled cortical impact/sham brain injury. At 24 hrs postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 μL) or phosphate-buffered saline (control group) were infused intracerebroventricularly contralateral to the injured side. Immunosuppression was achieved by cyclosporine A (10 mg/kg intraperitoneally).
MEASUREMENTS AND MAIN RESULTS:After controlled cortical impact, human umbilical cord blood mesenchymal stem cell transplantation induced an early and long-lasting improvement in sensorimotor functions assessed by neuroscore and beam walk tests. One month postinjury, human umbilical cord blood mesenchymal stem cell mice showed attenuated learning dysfunction at the Morris water maze and reduced contusion volume compared with controls. Hoechst positive human umbilical cord blood mesenchymal stem cells homed to lesioned tissue as early as 1 wk after injury in 67% of mice and survived in the injured brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased brain-derived neurotrophic factor concentration into the lesioned tissue, restoring its expression close to the levels observed in sham operated mice. By 7 days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a nonphagocytic activation of microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a marker of microglia/macrophage activation/recruitment) associated with a decrease (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a decrease of glial fibrillary acidic protein positivity in the scar region compared with control mice.
CONCLUSIONS:These findings indicate that human umbilical cord blood mesenchymal stem cells stimulate the injured brain and evoke trophic events, microglia/macrophage phenotypical switch, and glial scar inhibitory effects that remodel the brain and lead to significant improvement of neu |
| doi_str_mv | 10.1097/CCM.0b013e31822629ba |
| format | Article |
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DESIGN:Prospective experimental study.
SETTING:Research laboratory.
SUBJECTS:Male C57Bl/6 mice.
INTERVENTIONS:Mice were subjected to controlled cortical impact/sham brain injury. At 24 hrs postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 μL) or phosphate-buffered saline (control group) were infused intracerebroventricularly contralateral to the injured side. Immunosuppression was achieved by cyclosporine A (10 mg/kg intraperitoneally).
MEASUREMENTS AND MAIN RESULTS:After controlled cortical impact, human umbilical cord blood mesenchymal stem cell transplantation induced an early and long-lasting improvement in sensorimotor functions assessed by neuroscore and beam walk tests. One month postinjury, human umbilical cord blood mesenchymal stem cell mice showed attenuated learning dysfunction at the Morris water maze and reduced contusion volume compared with controls. Hoechst positive human umbilical cord blood mesenchymal stem cells homed to lesioned tissue as early as 1 wk after injury in 67% of mice and survived in the injured brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased brain-derived neurotrophic factor concentration into the lesioned tissue, restoring its expression close to the levels observed in sham operated mice. By 7 days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a nonphagocytic activation of microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a marker of microglia/macrophage activation/recruitment) associated with a decrease (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a decrease of glial fibrillary acidic protein positivity in the scar region compared with control mice.
CONCLUSIONS:These findings indicate that human umbilical cord blood mesenchymal stem cells stimulate the injured brain and evoke trophic events, microglia/macrophage phenotypical switch, and glial scar inhibitory effects that remodel the brain and lead to significant improvement of neurologic outcome.</description><identifier>ISSN: 0090-3493</identifier><identifier>EISSN: 1530-0293</identifier><identifier>DOI: 10.1097/CCM.0b013e31822629ba</identifier><identifier>PMID: 21725237</identifier><identifier>CODEN: CCMDC7</identifier><language>eng</language><publisher>Hagerstown, MD: by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Behavior, Animal ; Biological and medical sciences ; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis ; Brain Injuries - complications ; Brain Injuries - pathology ; Brain Injuries - therapy ; Cognition Disorders - etiology ; Cognition Disorders - prevention & control ; Cord Blood Stem Cell Transplantation ; Humans ; Intensive care medicine ; Learning Disorders - etiology ; Learning Disorders - prevention & control ; Male ; Medical sciences ; Mesenchymal Stem Cell Transplantation ; Mice ; Prospective Studies ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Critical care medicine, 2011-11, Vol.39 (11), p.2501-2510</ispartof><rights>2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3817-6c80bec17b16fab56536e9c44772ced1b4eb4ced25189d1846313bfd74bb011c3</citedby><cites>FETCH-LOGICAL-c3817-6c80bec17b16fab56536e9c44772ced1b4eb4ced25189d1846313bfd74bb011c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24725560$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21725237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zanier, Elisa R</creatorcontrib><creatorcontrib>Montinaro, Mery</creatorcontrib><creatorcontrib>Vigano, Mariele</creatorcontrib><creatorcontrib>Villa, Pia</creatorcontrib><creatorcontrib>Fumagalli, Stefano</creatorcontrib><creatorcontrib>Pischiutta, Francesca</creatorcontrib><creatorcontrib>Longhi, Luca</creatorcontrib><creatorcontrib>Leoni, Matteo L</creatorcontrib><creatorcontrib>Rebulla, Paolo</creatorcontrib><creatorcontrib>Stocchetti, Nino</creatorcontrib><creatorcontrib>Lazzari, Lorenza</creatorcontrib><creatorcontrib>De Simoni, Maria-Grazia</creatorcontrib><title>Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma</title><title>Critical care medicine</title><addtitle>Crit Care Med</addtitle><description>OBJECTIVE:To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant changes in the environment in which they are infused.
DESIGN:Prospective experimental study.
SETTING:Research laboratory.
SUBJECTS:Male C57Bl/6 mice.
INTERVENTIONS:Mice were subjected to controlled cortical impact/sham brain injury. At 24 hrs postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 μL) or phosphate-buffered saline (control group) were infused intracerebroventricularly contralateral to the injured side. Immunosuppression was achieved by cyclosporine A (10 mg/kg intraperitoneally).
MEASUREMENTS AND MAIN RESULTS:After controlled cortical impact, human umbilical cord blood mesenchymal stem cell transplantation induced an early and long-lasting improvement in sensorimotor functions assessed by neuroscore and beam walk tests. One month postinjury, human umbilical cord blood mesenchymal stem cell mice showed attenuated learning dysfunction at the Morris water maze and reduced contusion volume compared with controls. Hoechst positive human umbilical cord blood mesenchymal stem cells homed to lesioned tissue as early as 1 wk after injury in 67% of mice and survived in the injured brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased brain-derived neurotrophic factor concentration into the lesioned tissue, restoring its expression close to the levels observed in sham operated mice. By 7 days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a nonphagocytic activation of microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a marker of microglia/macrophage activation/recruitment) associated with a decrease (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a decrease of glial fibrillary acidic protein positivity in the scar region compared with control mice.
CONCLUSIONS:These findings indicate that human umbilical cord blood mesenchymal stem cells stimulate the injured brain and evoke trophic events, microglia/macrophage phenotypical switch, and glial scar inhibitory effects that remodel the brain and lead to significant improvement of neurologic outcome.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Behavior, Animal</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis</subject><subject>Brain Injuries - complications</subject><subject>Brain Injuries - pathology</subject><subject>Brain Injuries - therapy</subject><subject>Cognition Disorders - etiology</subject><subject>Cognition Disorders - prevention & control</subject><subject>Cord Blood Stem Cell Transplantation</subject><subject>Humans</subject><subject>Intensive care medicine</subject><subject>Learning Disorders - etiology</subject><subject>Learning Disorders - prevention & control</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mice</subject><subject>Prospective Studies</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><issn>0090-3493</issn><issn>1530-0293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkMtq3DAUQEVpaSbT_kEp2pSunN4ryZa9LEOaBBJKoV0LSb5mnEh2KtkM-fsqZNJABEIPzn0dxj4hnCF0-ttud3MGDlCSxFaIRnTOvmEbrCVUIDr5lm0AOqik6uQJO835FgBVreV7diJQi1pIvWG_LtdoJ75GN4bR28D9nHruwjz3PFKmye8fYvnOC0XuKYTM79O8kF94HD1xl-w4cTsslPiSbEn2gb0bbMj08Xhu2Z8f5793l9X1z4ur3ffryssWddX4Fhx51A6bwbq6qWVDnVdKa-GpR6fIqXIRNbZdj61qJEo39Fq5MjR6uWVfn_KWfv6ulBcTx_zYoZ1oXrPpoG41tMXHlqkn0qc550SDuU9jtOnBIJhHl6a4NK9dlrDPxwKri9T_D3qWV4AvR8Dmom5IdvJjfuFU4eoGXuof5lA85buwHiiZPdmw7A2UJYVqKlHGQiyvqmzU8h9B3I0Q</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Zanier, Elisa R</creator><creator>Montinaro, Mery</creator><creator>Vigano, Mariele</creator><creator>Villa, Pia</creator><creator>Fumagalli, Stefano</creator><creator>Pischiutta, Francesca</creator><creator>Longhi, Luca</creator><creator>Leoni, Matteo L</creator><creator>Rebulla, Paolo</creator><creator>Stocchetti, Nino</creator><creator>Lazzari, Lorenza</creator><creator>De Simoni, Maria-Grazia</creator><general>by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</general><general>Lippincott Williams & Wilkins</general><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>7X8</scope></search><sort><creationdate>201111</creationdate><title>Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma</title><author>Zanier, Elisa R ; Montinaro, Mery ; Vigano, Mariele ; Villa, Pia ; Fumagalli, Stefano ; Pischiutta, Francesca ; Longhi, Luca ; Leoni, Matteo L ; Rebulla, Paolo ; Stocchetti, Nino ; Lazzari, Lorenza ; De Simoni, Maria-Grazia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3817-6c80bec17b16fab56536e9c44772ced1b4eb4ced25189d1846313bfd74bb011c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Behavior, Animal</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis</topic><topic>Brain Injuries - complications</topic><topic>Brain Injuries - pathology</topic><topic>Brain Injuries - therapy</topic><topic>Cognition Disorders - etiology</topic><topic>Cognition Disorders - prevention & control</topic><topic>Cord Blood Stem Cell Transplantation</topic><topic>Humans</topic><topic>Intensive care medicine</topic><topic>Learning Disorders - etiology</topic><topic>Learning Disorders - prevention & control</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mice</topic><topic>Prospective Studies</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zanier, Elisa R</creatorcontrib><creatorcontrib>Montinaro, Mery</creatorcontrib><creatorcontrib>Vigano, Mariele</creatorcontrib><creatorcontrib>Villa, Pia</creatorcontrib><creatorcontrib>Fumagalli, Stefano</creatorcontrib><creatorcontrib>Pischiutta, Francesca</creatorcontrib><creatorcontrib>Longhi, Luca</creatorcontrib><creatorcontrib>Leoni, Matteo L</creatorcontrib><creatorcontrib>Rebulla, Paolo</creatorcontrib><creatorcontrib>Stocchetti, Nino</creatorcontrib><creatorcontrib>Lazzari, Lorenza</creatorcontrib><creatorcontrib>De Simoni, Maria-Grazia</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zanier, Elisa R</au><au>Montinaro, Mery</au><au>Vigano, Mariele</au><au>Villa, Pia</au><au>Fumagalli, Stefano</au><au>Pischiutta, Francesca</au><au>Longhi, Luca</au><au>Leoni, Matteo L</au><au>Rebulla, Paolo</au><au>Stocchetti, Nino</au><au>Lazzari, Lorenza</au><au>De Simoni, Maria-Grazia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma</atitle><jtitle>Critical care medicine</jtitle><addtitle>Crit Care Med</addtitle><date>2011-11</date><risdate>2011</risdate><volume>39</volume><issue>11</issue><spage>2501</spage><epage>2510</epage><pages>2501-2510</pages><issn>0090-3493</issn><eissn>1530-0293</eissn><coden>CCMDC7</coden><abstract>OBJECTIVE:To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant changes in the environment in which they are infused.
DESIGN:Prospective experimental study.
SETTING:Research laboratory.
SUBJECTS:Male C57Bl/6 mice.
INTERVENTIONS:Mice were subjected to controlled cortical impact/sham brain injury. At 24 hrs postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 μL) or phosphate-buffered saline (control group) were infused intracerebroventricularly contralateral to the injured side. Immunosuppression was achieved by cyclosporine A (10 mg/kg intraperitoneally).
MEASUREMENTS AND MAIN RESULTS:After controlled cortical impact, human umbilical cord blood mesenchymal stem cell transplantation induced an early and long-lasting improvement in sensorimotor functions assessed by neuroscore and beam walk tests. One month postinjury, human umbilical cord blood mesenchymal stem cell mice showed attenuated learning dysfunction at the Morris water maze and reduced contusion volume compared with controls. Hoechst positive human umbilical cord blood mesenchymal stem cells homed to lesioned tissue as early as 1 wk after injury in 67% of mice and survived in the injured brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased brain-derived neurotrophic factor concentration into the lesioned tissue, restoring its expression close to the levels observed in sham operated mice. By 7 days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a nonphagocytic activation of microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a marker of microglia/macrophage activation/recruitment) associated with a decrease (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a decrease of glial fibrillary acidic protein positivity in the scar region compared with control mice.
CONCLUSIONS:These findings indicate that human umbilical cord blood mesenchymal stem cells stimulate the injured brain and evoke trophic events, microglia/macrophage phenotypical switch, and glial scar inhibitory effects that remodel the brain and lead to significant improvement of neurologic outcome.</abstract><cop>Hagerstown, MD</cop><pub>by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</pub><pmid>21725237</pmid><doi>10.1097/CCM.0b013e31822629ba</doi><tpages>10</tpages></addata></record> |
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| ispartof | Critical care medicine, 2011-11, Vol.39 (11), p.2501-2510 |
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| language | eng |
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| source | MEDLINE; Journals@Ovid Complete |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Behavior, Animal Biological and medical sciences Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis Brain Injuries - complications Brain Injuries - pathology Brain Injuries - therapy Cognition Disorders - etiology Cognition Disorders - prevention & control Cord Blood Stem Cell Transplantation Humans Intensive care medicine Learning Disorders - etiology Learning Disorders - prevention & control Male Medical sciences Mesenchymal Stem Cell Transplantation Mice Prospective Studies Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma |
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