Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
Elima Agatieva,
Said Ksembaev,
Mikhail Sokolov,
Vage Markosyan,
Ilnaz Gazizov,
Dmitry Tsyplakov,
Maxim Shmarov,
Irina Tutykhina,
Boris Naroditsky,
Denis Logunov,
Oskar Pozdeev,
Lidiya Morozova,
Kamilya Yapparova,
Rustem Islamov
Affiliations
Elima Agatieva
Department of Maxillofacial Surgery and Surgical Dentistry, Kazan State Medical University, 420012 Kazan, Russia
Said Ksembaev
Department of Maxillofacial Surgery and Surgical Dentistry, Kazan State Medical University, 420012 Kazan, Russia
Mikhail Sokolov
Department of Operative Surgery and Topographic Anatomy, Kazan State Medical University, 420012 Kazan, Russia
Vage Markosyan
Department of Operative Surgery and Topographic Anatomy, Kazan State Medical University, 420012 Kazan, Russia
Ilnaz Gazizov
Department of Operative Surgery and Topographic Anatomy, Kazan State Medical University, 420012 Kazan, Russia
Dmitry Tsyplakov
Department of Pathology, Kazan State Medical University, 420012 Kazan, Russia
Maxim Shmarov
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Irina Tutykhina
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Boris Naroditsky
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Denis Logunov
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Oskar Pozdeev
Department of Microbiology, Kazan State Medical Academy, 420012 Kazan, Russia
Lidiya Morozova
Department of Microbiology, Kazan State Medical Academy, 420012 Kazan, Russia
Kamilya Yapparova
Department of Medical Biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Rustem Islamov
Department of Medical Biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
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.
