Open AccessMESENCHYMAL STEM CELLS ENHANCE IMMUNE RESPONSE AND PROTECTMICE AGAINST LETHAL HERPES VIRAL INFECTION
Author(s) -
Р. Р. Климова,
Ekaterina Momotyuk,
N. A. Demidova,
E. I. Yarigina,
А А Кущ
Publication year - 2018
Publication title -
voprosy virusologii
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.151
H-Index - 15
eISSN - 2411-2097
pISSN - 0507-4088
DOI - 10.18821/0507-4088-2018-63-6-261-267
Subject(s) - mesenchymal stem cell , immune system , virology , biology , viral infection , host response , immunology , virus , microbiology and biotechnology
The objective of this study was to evaluate immunoregulatory and protective potential of mesenchymal stem cells (MSC) in a mouse model of lethal HSV1 infection. MSC were isolated from bone marrow of DBA mice and cultured in asks with DMEM containing 10% FBS, insulin, transferrin, selenite, fbroblast growth factor, glutaminе and gentamicin. Antiviral activity was tested on HSV1-infected Vero cells. In vivo experiments were performed on DBA mice divided into 5 groups (10 animals each): group 1, intact (naïve) mice; group 2, intravenous (iv) MSC injection; group 3, ntraperitoneal infection with 20 LD50 HSV1 followed by MSC injection; group 4, HSV1 infection followed by acyclovir (ACV) injection; group 5, HSV1 infection and iv injection of saline. Isolated cells were consistent with MSC morphologically, by adhesive ability and surface receptors. Conditioned media from MSC collected after 4-5 passages inhibited HSV1 infection in vitro by 64-70% and contained IL-6 and TNF-α, whose concentrations were 5- and 20-fold higher, respectively, than in the control. MSC and ACV injections protected 70% and 60% of DBA mice, respectively, compared with the control (group 5, 10% survival). High activity of virus neutralizing anti-HSV1 antibodies and activation of T cell proliferation were observed in survived mice from group 3. Serum levels of IL-6 and TNF-α in these mice were lower and that of INF-γ much higher than in agonizing animals of this group (Р<0.05). These fndings indicate that MSC therapy is a prospective approach to the development of new effective management of generalized HSV1 infection.