Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord
Here we describe transplantation of olfactory ensheathing cells (OECs) or Schwann cells derived from transgenic pigs expressing the human complement inhibitory protein, CD59 (hCD59), into transected dorsal column lesions of the spinal cord of the immunosuppressed rat to induce axonal regeneration. N...
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| Veröffentlicht in: | Nature biotechnology 2000-09, Vol.18 (9), p.949-953 |
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| creator | Kocsis, Jeffery D Imaizumi, Toshio Lankford, Karen L Burton, Willis V Fodor, William L |
| description | Here we describe transplantation of olfactory ensheathing cells (OECs) or Schwann cells derived from transgenic pigs expressing the human complement inhibitory protein, CD59 (hCD59), into transected dorsal column lesions of the spinal cord of the immunosuppressed rat to induce axonal regeneration. Non-transplanted lesion-controlled rats exhibited no impulse conduction across the transection site, whereas in animals receiving transgenic pig OECs or Schwann cells impulse conduction was restored across and beyond the lesion site for more than a centimeter. Cell labeling indicated that the donor cells migrated into the denervated host tract. Conduction velocity measurements showed that the regenerated axons conducted impulses faster than normal axons. By morphological analysis, the axons seemed thickly myelinated with a peripheral pattern of myelin expected from the donor cell type. These results indicate that xenotranplantation of myelin-forming cells from pigs genetically altered to reduce the hyperacute response in humans are able to induce elongative axonal regeneration and remyelination and restore impulse conduction across the transected spinal cord. |
| doi_str_mv | 10.1038/79432 |
| format | Article |
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Non-transplanted lesion-controlled rats exhibited no impulse conduction across the transection site, whereas in animals receiving transgenic pig OECs or Schwann cells impulse conduction was restored across and beyond the lesion site for more than a centimeter. Cell labeling indicated that the donor cells migrated into the denervated host tract. Conduction velocity measurements showed that the regenerated axons conducted impulses faster than normal axons. By morphological analysis, the axons seemed thickly myelinated with a peripheral pattern of myelin expected from the donor cell type. These results indicate that xenotranplantation of myelin-forming cells from pigs genetically altered to reduce the hyperacute response in humans are able to induce elongative axonal regeneration and remyelination and restore impulse conduction across the transected spinal cord.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/79432</identifier><identifier>PMID: 10973214</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animals ; Animals, Genetically Modified ; Antibodies ; Axons - physiology ; Axons - ultrastructure ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; CD59 antigen ; CD59 Antigens - genetics ; CD59 Antigens - metabolism ; Cell Separation ; Cells ; Electrophysiology ; Flow Cytometry ; Fluorescent Antibody Technique, Indirect ; Fundamental and applied biological sciences. Psychology ; Health. Pharmaceutical industry ; Hogs ; Humans ; Immunosuppression Therapy ; Industrial applications and implications. Economical aspects ; Lesions ; Life Sciences ; Miscellaneous ; Models, Biological ; Nervous system ; olfactory ensheathing cells ; Olfactory Nerve - cytology ; Olfactory Nerve - metabolism ; Proteins ; Rats ; Rats, Wistar ; Regeneration ; Schwann Cells - metabolism ; Sciatic Nerve - metabolism ; Spinal cord ; Spinal Cord - physiology ; Spinal Cord - ultrastructure ; Swine ; Transgenes ; Transplantation, Heterologous - methods ; Transplants & implants</subject><ispartof>Nature biotechnology, 2000-09, Vol.18 (9), p.949-953</ispartof><rights>Nature America Inc. 2000</rights><rights>2000 INIST-CNRS</rights><rights>COPYRIGHT 2000 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c745t-58ca5e8b194a4c8f300d0bd367760626b9b92baa5053de5c60d8a15deb6432193</citedby><cites>FETCH-LOGICAL-c745t-58ca5e8b194a4c8f300d0bd367760626b9b92baa5053de5c60d8a15deb6432193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1504790$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10973214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kocsis, Jeffery D</creatorcontrib><creatorcontrib>Imaizumi, Toshio</creatorcontrib><creatorcontrib>Lankford, Karen L</creatorcontrib><creatorcontrib>Burton, Willis V</creatorcontrib><creatorcontrib>Fodor, William L</creatorcontrib><title>Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>Here we describe transplantation of olfactory ensheathing cells (OECs) or Schwann cells derived from transgenic pigs expressing the human complement inhibitory protein, CD59 (hCD59), into transected dorsal column lesions of the spinal cord of the immunosuppressed rat to induce axonal regeneration. Non-transplanted lesion-controlled rats exhibited no impulse conduction across the transection site, whereas in animals receiving transgenic pig OECs or Schwann cells impulse conduction was restored across and beyond the lesion site for more than a centimeter. Cell labeling indicated that the donor cells migrated into the denervated host tract. Conduction velocity measurements showed that the regenerated axons conducted impulses faster than normal axons. By morphological analysis, the axons seemed thickly myelinated with a peripheral pattern of myelin expected from the donor cell type. These results indicate that xenotranplantation of myelin-forming cells from pigs genetically altered to reduce the hyperacute response in humans are able to induce elongative axonal regeneration and remyelination and restore impulse conduction across the transected spinal cord.</description><subject>Agriculture</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Antibodies</subject><subject>Axons - physiology</subject><subject>Axons - ultrastructure</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>CD59 antigen</subject><subject>CD59 Antigens - genetics</subject><subject>CD59 Antigens - metabolism</subject><subject>Cell Separation</subject><subject>Cells</subject><subject>Electrophysiology</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Health. Pharmaceutical industry</subject><subject>Hogs</subject><subject>Humans</subject><subject>Immunosuppression Therapy</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Lesions</subject><subject>Life Sciences</subject><subject>Miscellaneous</subject><subject>Models, Biological</subject><subject>Nervous system</subject><subject>olfactory ensheathing cells</subject><subject>Olfactory Nerve - cytology</subject><subject>Olfactory Nerve - metabolism</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Regeneration</subject><subject>Schwann Cells - metabolism</subject><subject>Sciatic Nerve - metabolism</subject><subject>Spinal cord</subject><subject>Spinal Cord - physiology</subject><subject>Spinal Cord - ultrastructure</subject><subject>Swine</subject><subject>Transgenes</subject><subject>Transplantation, Heterologous - methods</subject><subject>Transplants & implants</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkttu1DAQhiMEoqX0FVBABcTFFjs-xTdIVcWhUqVKnMSd5TiT1FXWTm0HtW-Pd7PqdnsByBe2Zr75bf8zRXGI0TFGpH4vJCXVo2IfM8oXmEv-OJ9RLRYIM75XPIvxCiHEKedPiz2MpCAVpvvF9S9wPgXt4jhol3Sy3pW-K9ehHpw15Wj70g-dNsmH2xJcvASdLq3rSwPDEMsx-KVPEEt9450eygC5DsIsZV2ZT2Uc7SplfGifF086PUQ43OwHxY9PH7-fflmcX3w-Oz05XxhBWVqw2mgGdYMl1dTUHUGoRU1LuBAc8Yo3spFVozVDjLTADEdtrTFroeHZCCzJQfFh1h2nZgmtAZf_NKgx2KUOt8prq3Yzzl6q3v9WFc-SAmeBtxuB4K8niEktbVx9WTvwU1S1EEzWtGaZfPNXUlQVkUiQf4JYcIHrteKrB-CVn0K2MKoqiyFByQo6nqFeD6Cs61aNNHm1sLTGO-hsjp9gmRsv80tzwbudgswkuEm9nmJUZ9--_j978XOXfT2zJvgYA3R3LmOkVtOp1tOZuRf3W3KPmscxA0cbQEejhy4PobFxyzFEhURbG2POuB7C1p2HF76cQafTFOBOyDUJ5dcrSSX5A4u5AvI</recordid><startdate>20000901</startdate><enddate>20000901</enddate><creator>Kocsis, Jeffery D</creator><creator>Imaizumi, Toshio</creator><creator>Lankford, Karen L</creator><creator>Burton, Willis V</creator><creator>Fodor, William L</creator><general>Nature Publishing Group US</general><general>Nature</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20000901</creationdate><title>Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord</title><author>Kocsis, Jeffery D ; Imaizumi, Toshio ; Lankford, Karen L ; Burton, Willis V ; Fodor, William L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c745t-58ca5e8b194a4c8f300d0bd367760626b9b92baa5053de5c60d8a15deb6432193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Agriculture</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Antibodies</topic><topic>Axons - physiology</topic><topic>Axons - ultrastructure</topic><topic>Bioinformatics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>CD59 antigen</topic><topic>CD59 Antigens - genetics</topic><topic>CD59 Antigens - metabolism</topic><topic>Cell Separation</topic><topic>Cells</topic><topic>Electrophysiology</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Fundamental and applied biological sciences. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kocsis, Jeffery D</au><au>Imaizumi, Toshio</au><au>Lankford, Karen L</au><au>Burton, Willis V</au><au>Fodor, William L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2000-09-01</date><risdate>2000</risdate><volume>18</volume><issue>9</issue><spage>949</spage><epage>953</epage><pages>949-953</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><coden>NABIF9</coden><abstract>Here we describe transplantation of olfactory ensheathing cells (OECs) or Schwann cells derived from transgenic pigs expressing the human complement inhibitory protein, CD59 (hCD59), into transected dorsal column lesions of the spinal cord of the immunosuppressed rat to induce axonal regeneration. Non-transplanted lesion-controlled rats exhibited no impulse conduction across the transection site, whereas in animals receiving transgenic pig OECs or Schwann cells impulse conduction was restored across and beyond the lesion site for more than a centimeter. Cell labeling indicated that the donor cells migrated into the denervated host tract. Conduction velocity measurements showed that the regenerated axons conducted impulses faster than normal axons. By morphological analysis, the axons seemed thickly myelinated with a peripheral pattern of myelin expected from the donor cell type. These results indicate that xenotranplantation of myelin-forming cells from pigs genetically altered to reduce the hyperacute response in humans are able to induce elongative axonal regeneration and remyelination and restore impulse conduction across the transected spinal cord.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>10973214</pmid><doi>10.1038/79432</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Agriculture Animals Animals, Genetically Modified Antibodies Axons - physiology Axons - ultrastructure Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology CD59 antigen CD59 Antigens - genetics CD59 Antigens - metabolism Cell Separation Cells Electrophysiology Flow Cytometry Fluorescent Antibody Technique, Indirect Fundamental and applied biological sciences. Psychology Health. Pharmaceutical industry Hogs Humans Immunosuppression Therapy Industrial applications and implications. Economical aspects Lesions Life Sciences Miscellaneous Models, Biological Nervous system olfactory ensheathing cells Olfactory Nerve - cytology Olfactory Nerve - metabolism Proteins Rats Rats, Wistar Regeneration Schwann Cells - metabolism Sciatic Nerve - metabolism Spinal cord Spinal Cord - physiology Spinal Cord - ultrastructure Swine Transgenes Transplantation, Heterologous - methods Transplants & implants |
| title | Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord |
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