{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:32:40Z","timestamp":1786739560611,"version":"build-2736575974"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases, neurotrauma, and stroke. In this study, using a mini pig model of spinal cord injury, we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    gene therapy. Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector (Ad5\/35F) that carried an enhanced green fluorescent protein (EGFP) reporter gene in the plastic blood bag. The day after blood donation, the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate. A week after gene-modified leucoconcentrate therapy, fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury. In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes. Thus, the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions. This paper presents a proof-of-concept of simple, safe and effective approach for personalized\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    gene therapy based on gene-modified leucoconcentrate autoinfusion. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee (approval No. 5) on May 27, 2014.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.290902","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T16:15:06Z","timestamp":1598285706000},"page":"357-361","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury"],"prefix":"10.4103","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-4636","authenticated-orcid":false,"given":"Rustem R.","family":"Islamov","sequence":"first","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farid V.","family":"Bashirov","sequence":"additional","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail E.","family":"Sokolov","sequence":"additional","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei A.","family":"Izmailov","sequence":"additional","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip O.","family":"Fadeev","sequence":"additional","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vage A.","family":"Markosyan","sequence":"additional","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Davleeva","sequence":"additional","affiliation":[{"name":"Kazan State Medical University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Zubkova","sequence":"additional","affiliation":[{"name":"Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim M.","family":"Smarov","sequence":"additional","affiliation":[{"name":"Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis Yu.","family":"Logunov","sequence":"additional","affiliation":[{"name":"Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris S.","family":"Naroditskyi","sequence":"additional","affiliation":[{"name":"Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilnur I.","family":"Salafutdinov","sequence":"additional","affiliation":[{"name":"Kazan Federal University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-5739","authenticated-orcid":false,"given":"Albert A.","family":"Rizvanov","sequence":"additional","affiliation":[{"name":"Kazan Federal University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramil G.","family":"Turaev","sequence":"additional","affiliation":[{"name":"The Republican Blood Center of the Ministry of Health of the Republic of Tatarstan, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,2]]},"reference":[{"key":"R1-20260525","doi-asserted-by":"crossref","first-page":"7499","DOI":"10.1073\/pnas.1017146108","article-title":"Adenovirus type-35 vectors block human CD4+ T-cell activation via CD46 ligation","volume":"108","author":"Adams","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R2-20260525","doi-asserted-by":"crossref","first-page":"737","DOI":"10.15252\/emmm.201707573","article-title":"Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products","volume":"9","author":"Aiuti","year":"2017","journal-title":"EMBO Mol Med"},{"key":"R3-20260525","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1126\/science.270.5235.475","article-title":"T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years","volume":"270","author":"Blaese","year":"1995","journal-title":"Science"},{"key":"R4-20260525","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1126\/science.1171242","article-title":"Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy","volume":"326","author":"Cartier","year":"2009","journal-title":"Science"},{"key":"R5-20260525","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.biopha.2018.09.138","article-title":"Gene therapy and type 1 diabetes mellitus","volume":"108","author":"Chellappan","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"R6-20260525","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/jnr.10303","article-title":"Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury","volume":"69","author":"Cheng","year":"2002","journal-title":"J Neurosci Res"},{"key":"R7-20260525","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/hum.2013.2527","article-title":"Adenovirus: The first effective in vivo gene delivery vector","volume":"25","author":"Crystal","year":"2014","journal-title":"Hum Gene Ther"},{"key":"R8-20260525","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19061776","article-title":"Translational regenerative therapies for chronic spinal cord injury","author":"Dalamagkas","year":"2018","journal-title":"Int J Mol Sci"},{"key":"R9-20260525","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1089\/hum.2004.15.1054","article-title":"Adenoviral serotype 5 vectors pseudotyped with fibers from subgroup D show modified tropism in vitro and in vivo","volume":"15","author":"Denby","year":"2004","journal-title":"Hum Gene Ther"},{"key":"R10-20260525","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1755-7682-3-30","article-title":"Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report","volume":"3","author":"Ichim","year":"2010","journal-title":"Int Arch Med"},{"key":"R11-20260525","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1007\/s12035-016-0017-x","article-title":"Tandem delivery of multiple therapeutic genes using umbilical cord blood cells improves symptomatic outcomes in ALS","volume":"54","author":"Islamov","year":"2017","journal-title":"Mol Neurobiol"},{"key":"R12-20260525","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neulet.2017.02.034","article-title":"A pilot study of cell-mediated gene therapy for spinal cord injury in mini pigs","volume":"644","author":"Islamov","year":"2017","journal-title":"Neurosci Lett"},{"key":"R13-20260525","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3389\/fphar.2017.00813","article-title":"Spinal cord molecular and cellular changes induced by adenoviral vector- and cell-mediated triple gene therapy after severe contusion","volume":"8","author":"Izmailov","year":"2017","journal-title":"Front Pharmacol"},{"key":"R14-20260525","doi-asserted-by":"crossref","first-page":"624","DOI":"10.3171\/2012.3.SPINE11970","article-title":"Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury: Laboratory investigation","volume":"16","author":"Jones","year":"2012","journal-title":"J Neurosurg Spine"},{"key":"R15-20260525","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/978-3-319-17121-0_73","article-title":"Personalized medicine: cell and gene therapy based on patient-specific iPSC-derived retinal pigment epithelium cells","volume":"854","author":"Li","year":"2016","journal-title":"Adv Exp Med Biol"},{"key":"R16-20260525","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jcyt.2012.09.005","article-title":"Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells","volume":"15","author":"Liu","year":"2013","journal-title":"Cytotherapy"},{"key":"R17-20260525","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/0042-6822(68)90122-0","article-title":"The polypeptides of adenovirus. II. Soluble proteins, cores, top components and the structure of the virion","volume":"36","author":"Maizel","year":"1968","journal-title":"Virology"},{"key":"R18-20260525","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.addr.2017.09.003","article-title":"Cell-mediated enzyme prodrug cancer therapies","volume":"118","author":"Mooney","year":"2017","journal-title":"Adv Drug Deliv Rev"},{"key":"R19-20260525","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.4103\/1673-5374.191213","article-title":"Genetically modified human umbilical cord blood cells as a promising strategy for treatment of spinal cord injury","volume":"11","author":"Mukhamedshina","year":"2016","journal-title":"Neural Regen Res"},{"key":"R20-20260525","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s13287-015-0202-2","article-title":"Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury","volume":"6","author":"Neirinckx","year":"2015","journal-title":"Stem Cell Res Ther"},{"key":"R21-20260525","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/jgm.526","article-title":"In vitro and in vivo characterisation of endothelial cell selective adenoviral vectors","volume":"6","author":"Nicklin","year":"2004","journal-title":"J Gene Med"},{"key":"R22-20260525","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/978-1-4939-7299-9_9","article-title":"Gene and cell therapy for \u03b2-thalassemia and sickle cell disease with induced pluripotent stem cells (iPSCs): the next frontier","volume":"1013","author":"Papapetrou","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"R23-20260525","doi-asserted-by":"crossref","first-page":"931","DOI":"10.4103\/1673-5374.250570","article-title":"Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases","volume":"14","author":"Qu","year":"2019","journal-title":"Neural Regen Res"},{"key":"R24-20260525","doi-asserted-by":"crossref","first-page":"100","DOI":"10.32607\/20758251-2011-3-3-100-106","article-title":"An efficient method for the delivery of the interleukin-2 gene to human hematopoietic cells using the fiber-modified recombinant adenovirus","volume":"3","author":"Rogozhin","year":"2011","journal-title":"Acta Naturae"},{"key":"R25-20260525","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fphar.2018.00111","article-title":"Triple-gene therapy for stroke: a proof-of-concept in vivo study in rats","volume":"9","author":"Sokolov","year":"2018","journal-title":"Front Pharmacol"},{"key":"R26-20260525","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.1523\/JNEUROSCI.19-14-05731.1999","article-title":"Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system","volume":"19","author":"Sondell","year":"1999","journal-title":"J Neurosci"},{"key":"R27-20260525","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1479-5876-8-75","article-title":"Safety evaluation of allogeneic umbilical cord blood mononuclear cell therapy for degenerative conditions","volume":"8","author":"Yang","year":"2010","journal-title":"J Transl Med"},{"key":"R28-20260525","first-page":"397","article-title":"Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury: Electrophysiological changes and long-term efficacy","volume":"8","author":"Yao","year":"2013","journal-title":"Neural Regen Res"},{"key":"R29-20260525","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1172\/JCI9369","article-title":"VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain","volume":"106","author":"Zhang","year":"2000","journal-title":"J Clin Invest"},{"key":"R30-20260525","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.drudis.2018.02.012","article-title":"Approved CAR T cell therapies: ice bucket challenges on glaring safety risks and long-term impacts","volume":"23","author":"Zheng","year":"2018","journal-title":"Drug Discov Today"},{"key":"R31-20260525","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.3727\/096368916X691411","article-title":"Phase I-II clinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury","volume":"25","author":"Zhu","year":"2016","journal-title":"Cell Transplant"}],"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.290902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:30:01Z","timestamp":1786735801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.290902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,24]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.4103\/1673-5374.290902","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,24]]},"assertion":[{"value":"2019-10-28","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-16","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}