Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury

作     者：Rustem R.Islamov Farid V.Bashirov Mikhail E.Sokolov Andrei A.Izmailov Filip O.Fadeev Vage A.Markosyan Maria A.Davleeva Olga V.Zubkova Maxim M.Smarov Denis Yu.Logunov Boris S.Naroditskyi Ilnur I.Salafutdinov Albert A.Rizvanov Ramil G.Turaev Rustem R. Islamov;Farid V. Bashirov;Mikhail E. Sokolov;Andrei A. Izmailov;Filip O. Fadeev;Vage A. Markosyan;Maria A. Davleeva;Olga V. Zubkova;Maxim M. Smarov;Denis Yu. Logunov;Boris S. Naroditskyi;Ilnur I. Salafutdinov;Albert A. Rizvanov;Ramil G. Turaev

作者机构：Kazan State Medical UniversityKazanRussia Gamaleya Research Institute of Epidemiology and MicrobiologyMoscowRussia Kazan Federal UniversityKazanRussia The Republican Blood Center of the Ministry of Health of the Republic of TatarstanKazanRussia 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2021年第16卷第2期

页      面：357-361页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：the Russian Science Foundation(No.16-15-00010 to RRI) the Russian Government Program of Competitive Growth of Kazan Federal University 

主　　题：chimeric Ad5/35F virus enhanced green fluorescent protein gene-modified leucoconcentrate mini pig peripheral blood personalized ex vivo gene therapy plastic blood bag spinal cord injury 

摘      要：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 *** 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 ex vivo gene *** obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F)that carried an enhanced green fluorescent protein(EGFP)reporter gene in the plastic blood *** 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 *** the spleen the groups of EGFP-positive cells located in the lymphoid follicles were *** vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by ***,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 *** paper presents a proof-of-concept of simple,safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate *** animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.5)on May 27,2014.