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Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats

Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known naïve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding LTF for di...

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Autores principales: Agatieva, Elima, Ksembaev, Said, Sokolov, Mikhail, Markosyan, Vage, Gazizov, Ilnaz, Tsyplakov, Dmitry, Shmarov, Maxim, Tutykhina, Irina, Naroditsky, Boris, Logunov, Denis, Pozdeev, Oskar, Morozova, Lidiya, Yapparova, Kamilya, Islamov, Rustem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823524/
https://www.ncbi.nlm.nih.gov/pubmed/33406760
http://dx.doi.org/10.3390/pharmaceutics13010058
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author Agatieva, Elima
Ksembaev, Said
Sokolov, Mikhail
Markosyan, Vage
Gazizov, Ilnaz
Tsyplakov, Dmitry
Shmarov, Maxim
Tutykhina, Irina
Naroditsky, Boris
Logunov, Denis
Pozdeev, Oskar
Morozova, Lidiya
Yapparova, Kamilya
Islamov, Rustem
author_facet Agatieva, Elima
Ksembaev, Said
Sokolov, Mikhail
Markosyan, Vage
Gazizov, Ilnaz
Tsyplakov, Dmitry
Shmarov, Maxim
Tutykhina, Irina
Naroditsky, Boris
Logunov, Denis
Pozdeev, Oskar
Morozova, Lidiya
Yapparova, Kamilya
Islamov, Rustem
author_sort Agatieva, Elima
collection PubMed
description Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known naïve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding LTF for direct and cell-mediated gene therapy of maxillofacial area phlegmon in rats. Abscesses were developed by injection of the purulent peritoneal exudate in the molar region of the medial surface of the mandible. At 3–4 days after phlegmon maturation, all rats received ceftriaxone and afterward were subcutaneously injected around the phlegmon with: (1) Ad5 carrying reporter gfp gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying LTF gene (Ad5-LTF group), (3) human umbilical cord blood mononuclear cells (UCBC) transduced with Ad5-GFP (UCBC + Ad5-GFP group), and (4) UCBC transduced with Ad5-LTF (UCBC + Ad5-LTF group). Control rats developed symptoms considered to be related to systemic inflammation and were euthanized at 4–5 days from the beginning of the treatment. Rats from therapeutic groups demonstrated wound healing and recovery from the fifth to seventh day based on the type of therapy. Histological investigation of cervical lymph nodes revealed purulent lymphadenitis in control rats and activated lymphatic tissue in rats from the UCBC + Ad5-LTF group. Our results propose that both approaches of LTF gene delivery are efficient for maxillofacial area phlegmon recovery in rats. However, earlier wound healing and better outcomes in cervical lymph node remodeling in the UCBC + Ad5-LTF group, as well as the lack of direct exposure of the viral vector to the organism, which may cause toxic and immunogenic effects, suggest the benefit of cell-mediated gene therapy.
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spelling pubmed-78235242021-01-24 Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats Agatieva, Elima Ksembaev, Said Sokolov, Mikhail Markosyan, Vage Gazizov, Ilnaz Tsyplakov, Dmitry Shmarov, Maxim Tutykhina, Irina Naroditsky, Boris Logunov, Denis Pozdeev, Oskar Morozova, Lidiya Yapparova, Kamilya Islamov, Rustem Pharmaceutics Article Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known naïve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding LTF for direct and cell-mediated gene therapy of maxillofacial area phlegmon in rats. Abscesses were developed by injection of the purulent peritoneal exudate in the molar region of the medial surface of the mandible. At 3–4 days after phlegmon maturation, all rats received ceftriaxone and afterward were subcutaneously injected around the phlegmon with: (1) Ad5 carrying reporter gfp gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying LTF gene (Ad5-LTF group), (3) human umbilical cord blood mononuclear cells (UCBC) transduced with Ad5-GFP (UCBC + Ad5-GFP group), and (4) UCBC transduced with Ad5-LTF (UCBC + Ad5-LTF group). Control rats developed symptoms considered to be related to systemic inflammation and were euthanized at 4–5 days from the beginning of the treatment. Rats from therapeutic groups demonstrated wound healing and recovery from the fifth to seventh day based on the type of therapy. Histological investigation of cervical lymph nodes revealed purulent lymphadenitis in control rats and activated lymphatic tissue in rats from the UCBC + Ad5-LTF group. Our results propose that both approaches of LTF gene delivery are efficient for maxillofacial area phlegmon recovery in rats. However, earlier wound healing and better outcomes in cervical lymph node remodeling in the UCBC + Ad5-LTF group, as well as the lack of direct exposure of the viral vector to the organism, which may cause toxic and immunogenic effects, suggest the benefit of cell-mediated gene therapy. MDPI 2021-01-04 /pmc/articles/PMC7823524/ /pubmed/33406760 http://dx.doi.org/10.3390/pharmaceutics13010058 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Agatieva, Elima
Ksembaev, Said
Sokolov, Mikhail
Markosyan, Vage
Gazizov, Ilnaz
Tsyplakov, Dmitry
Shmarov, Maxim
Tutykhina, Irina
Naroditsky, Boris
Logunov, Denis
Pozdeev, Oskar
Morozova, Lidiya
Yapparova, Kamilya
Islamov, Rustem
Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
title Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
title_full Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
title_fullStr Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
title_full_unstemmed Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
title_short Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
title_sort evaluation of direct and cell-mediated lactoferrin gene therapy for the maxillofacial area abscesses in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823524/
https://www.ncbi.nlm.nih.gov/pubmed/33406760
http://dx.doi.org/10.3390/pharmaceutics13010058
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