Introduction: The studies of MSCs therapeutic action have been conducted over the past 20 years for a variety of human pathologies, both in model experiments in animals and in clinical trials. However, there are very few studies on the effects of MSCs in viral infections. Thus the present work aimed to study the effects of MSCs administration at the very beginning of the acute phase on the course of influenza virus-induced pneumonia in mice.
Methodology: Mice were inoculated intranasally by mouse-adapted influenza virus strain A/FM/1/47/H1N1. The virus infectious dose was 4,0 1g LD50. The next day, mice from experimental groups were injected with human umbilical cord MSCs via intravenous, intraperitoneal, or intranasal routes. The doses of MCS were 1x106, 2x105, and 2x104 cells per animal. The results were evaluated by: the survival rate of experimental animals compared with controls, the viremia, the state of internal organs, and their histopathological analysis.
Results: In the virus control group, all infected mice died 6 to 11 days p.i. While in the experimental group with intravenous administration of 1x106 MSCs 20% of the animals remained alive. In the experimental group administered with 2x105 MSCs survival increased to 40%. However, dose reduction to 2x104 MSCs led to an earlier onset of the death, and the survival rate dropped to zero. The survival rate in experimental groups with intraperitoneal injection of 1x106 or 2x105 of MSCs was 20%. On the contrary, the experimental group that received 2x104 MSCs via the intraperitoneal route exhibited the same survival rate as the group with the 2x104 MSCs administered parenterally. All mice in the group were dead in the same time frame. In the group administered 1x106 MSCs, the death of animals began already on the third day and ended in complete death of animals. However, doses of 2x105 and 2x104 MSCs provided 40% survival. Histopathological studies revealed that the lungs in dead animals from the experimental groups administered with MSCs were elastically compacted. Internal organs had macroscopic signs of acute venous plethora in the vessels of the systemic circulation. A morphological study of lung tissues in dead animals with all types of administration and doses of MSCs showed a general picture of lesions: hyperplasia of broncho-associated lymphoid tissue; infiltration by lymphoid cells of the peribronchial tissue; the presence of lymphoid cells in the alveoli; and abundance of lymphoid cells in the lumen of the bronchi up to the obturation of these lumens. There was proliferation and infiltration of lymphoid cells in the respiratory sections of the lungs; dystrophic - destructive changes in the cells of the tissues of the organ; filling of the lungs and bronchi with serous-vascular exudate.
Conclusion: Thus, the results demonstrated that MSCs could increase survival in the lethal influenza virus-induced pneumonia model. The doses of MSCs and their administration routes were of decisive importance. The effectiveness of intranasal administration of MSCs was demonstrated. The administration of MSCs at an early stage of the acute phase of influenza virus-induced pneumonia changes the course of the disease.