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
Department of Maxillofacial Surgery and Surgical Dentistry, Kazan State Medical University, 420012 Kazan, Russia.
Department of Operative Surgery and Topographic Anatomy, Kazan State Medical University, 420012 Kazan, Russia.
Pharmaceutics. 2021 Jan 4;13(1):58. doi: 10.3390/pharmaceutics13010058.
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 gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying 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 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.
对抗菌治疗产生耐药性需要发现治疗传染病的新方法。乳铁蛋白（LTF）是一种著名的天然一线防御蛋白。在本研究中，我们建议使用携带编码LTF的人类基因的腺病毒载体（Ad5）对大鼠颌面部蜂窝织炎进行直接和细胞介导的基因治疗。通过在下颌骨内侧面磨牙区域注射脓性腹腔渗出液形成脓肿。在蜂窝织炎成熟后3 - 4天，所有大鼠接受头孢曲松治疗，随后在蜂窝织炎周围皮下注射：（1）携带编码绿色荧光蛋白的报告基因的Ad5（Ad5 - GFP对照组），（2）携带LTF基因的Ad5（Ad5 - LTF组），（3）用Ad5 - GFP转导的人脐带血单个核细胞（UCBC + Ad5 - GFP组），以及（4）用Ad5 - LTF转导的UCBC（UCBC + Ad5 - LTF组）。对照大鼠出现被认为与全身炎症相关的症状，并在治疗开始后4 - 5天实施安乐死。治疗组的大鼠根据治疗类型在第5至7天显示出伤口愈合和恢复。颈部淋巴结的组织学研究显示，对照大鼠有脓性淋巴结炎，而UCBC + Ad5 - LTF组的大鼠有活化的淋巴组织。我们的结果表明，两种基因递送方法对大鼠颌面部蜂窝织炎的恢复都是有效的。然而，UCBC + Ad5 - LTF组伤口愈合更早，颈部淋巴结重塑效果更好，以及病毒载体未直接暴露于机体（这可能会引起毒性和免疫原性效应），表明细胞介导的基因治疗具有优势。
