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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Pharmaceutics
• Subjects: maxillofacial area phlegmon; rat; gene therapy; adenoviral vector; human umbilical cord blood mononuclear cell; lactoferrin gene
• Online Access: https://www.mdpi.com/1999-4923/13/1/58

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 <i>gfp</i> gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying <i>LTF</i> 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 <i>LTF</i> 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.