USE OF MESENCHYMAL STEM CELLS IN COMPLEX TREATMENT OF DRUG-RESISTANT RENAL TUBERCULOSIS (EXPERIMENTAL STUDY WITH MORPHOLOGICAL CONTROL)

DOI: https://doi.org/10.29296/24999490-2023-05-04

T.I. Vinogradova(1), D.S. Esmedlyayeva(1), M.E. Dyakova(1), A.N. Muravyev(1), A.N. Remezova(1), B.M. Ariel(1),
E.O. Bogdanova(1), M.Z. Dogonadze(1), N.V. Zabolotnykh(1), N.Yu. Yudintseva(2), V.O. Polyakova(1), P.K. Yablonskiy(1, 3)
1-FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia,
Ligovsky Ave., 2–4, St. Petersburg, 191036, Russian Federation;
2-FGBUN Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky pr., 4, St. Petersburg, 194064, Russian Federation;
3-St. Petersburg State University, Russian Federation, Universitetskaya nab., 7/9, St. Petersburg, 199034, Russian Federation

Introduction. The use of mesenchymal stem cells (MSCs) is recognized as a promising direction for the treatment of diseases with a predominance of inflammation and sclerosis in the pathogenesis, which includes nephrotuberculosis (NT). Target. Studying the effectiveness of using MSCs in the complex treatment of experimental renal tuberculosis caused by a multidrug-resistant pathogen strain, and assessing the effect of cell therapy on the nature of reparative processes. Material and methods. NT with MDR was modeled in rabbits by inoculating the renal parenchyma cortex with a suspension of the clinical strain 5582 of Mycobacterium tuberculosis genotype Beijing (106 mycobacteria/0.2 ml). There were 3 groups: 1st (n=6) – infection control (infected, untreated); 2nd (n=7) – anti-tuberculosis therapy – ethambutol, bedaquiline, perchlozone, linezolid; 3rd main group (n=7) – rabbits 2 months after the start of chemotherapy were injected with a single suspension of 5×107 MSCs/2 ml PBS into the lateral vein of the ear. NT was confirmed by the results of Diaskintest® and computed tomography (CT), and the presence of viable MSCs by confocal microscopy with RKN-26 dye. A histological and morphometric study of the kidneys was carried out. We used the Statistica 7.0 package Results. The development of NT was confirmed by positive results of Diaskintest® and CT data (18 and 30 days after infection, respectively). 3 months after infection, only in group 1, foci of specific inflammation remained in the kidney tissue and pronounced glomerular changes were noted. In rabbits of the 3rd group, compared to the 2nd group, a low width of the medulla was revealed, as well as parameters of the area of interstitial fibrosis and collagen area, and higher values of glomerular cellularity. Conclusion. The participation of MSCs in complex therapy of NT led to a complete regression of specific inflammation in the kidney tissues, acceleration of reparative processes, and contributed to the preservation of the filtration capacity of the kidneys and the efficiency of urine excretion.
Keywords: 
mesenchymal stem cells, experimental nephrotuberculosis, multidrug resistance of mycobacteria, reparative reaction
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