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Extrapulmonary tuberculosis with a renal involvement can be a manifestation of a disseminated infection that requires therapeutic intervention, particularly with a decrease in efficacy of conventional regimens. In the present study, we investigated the therapeutic potency of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in the complex anti-tuberculosis treatment (ATT). A rabbit model of renal tuberculosis (rTB) was constructed by injecting of the standard strain Mycobacterium tuberculosis H37Rv into the cortical layer of the kidney parenchyma. Isolated rabbit MSC-EVs were intravenously administered once as an addition to standard ATT (isoniazid, pyrazinamide, and ethambutol). The therapeutic efficacy was assessed by analyzing changes of blood biochemical biomarkers and levels of anti- and pro-inflammatory cytokines as well as by renal computed tomography with subsequent histological and morphometric examination. The therapeutic effect of therapy with MSC-EVs was shown by ELISA method that confirmed a statistically significant increase of the anti-inflammatory and decrease of pro-inflammatory cytokines as compared to conventional treatment. In addition, there is a positive trend in increase of ALP level, animal weigh, and normalization of ADA activity that can indicate an improvement of kidney state. A significant reduction of the area of specific and interstitial inflammation indicated positive affect of MSC-EVs that suggests a shorter duration of ATT. The number of MSC-EVs proteins (as identified by mass-spectometry analysis) with anti-microbial, anti-inflammatory and immunoregulatory functions reduced the level of the inflammatory response and the severity of kidney damage (further proved by morphometric analysis). In conclusion, MSC-EVs can be a promising tool for the complex treatment of various infectious diseases, in particularly rTB.

Titel:	Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.
Autor/in / Beteiligte Person:	Yudintceva, N ; Bobkov, D ; Sulatsky, M ; Mikhailova, N ; Oganesyan, E ; Vinogradova, T ; Muraviov, A ; Remezova, A ; Bogdanova, E ; Garapach, I ; Maslak, O ; Esmedlyaeva, D ; Dyakova, M ; Yablonskiy, P ; Ziganshin, R ; Kovalchuk, S ; Blum, N ; Sonawane, SH ; Sonawane, A ; Behl, A ; Singh, Shailja ; Shevtsov, M
Link:	Full Text Finder (Volltext)
Zeitschrift:	Scientific reports, Jg. 14 (2024-02-24), Heft 1, S. 4495
Veröffentlichung:	London : Nature Publishing Group, copyright 2011-, 2024
Medientyp:	academicJournal
ISSN:	2045-2322 (electronic)
DOI:	10.1038/s41598-024-54992-z
Schlagwort:	Animals Rabbits Cytokines metabolism Anti-Inflammatory Agents therapeutic use Anti-Inflammatory Agents metabolism Tuberculosis, Renal metabolism Extracellular Vesicles metabolism Mesenchymal Stem Cells metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Sci Rep] 2024 Feb 24; Vol. 14 (1), pp. 4495. <i>Date of Electronic Publication: </i>2024 Feb 24. MeSH Terms: Tuberculosis, Renal* / metabolism ; Extracellular Vesicles* / metabolism ; Mesenchymal Stem Cells* / metabolism ; Animals ; Rabbits ; Cytokines / metabolism ; Anti-Inflammatory Agents / therapeutic use ; Anti-Inflammatory Agents / metabolism References: Am J Physiol. 1997 Dec;273(6):F849-56. (PMID: 9435672) ; Front Immunol. 2018 Jun 07;9:888. (PMID: 29930549) ; Lancet Microbe. 2023 Jan;4(1):e20. (PMID: 36521512) ; Biomater Res. 2016 Aug 05;20:21. (PMID: 27499886) ; J Extracell Vesicles. 2023 Jul;12(7):e12334. (PMID: 37357686) ; Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12123-8. (PMID: 14517352) ; Sci Rep. 2019 Mar 14;9(1):4468. (PMID: 30872726) ; Nat Rev Immunol. 2001 Oct;1(1):20-30. (PMID: 11905811) ; Nat Rev Immunol. 2010 Mar;10(3):170-81. 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(PMID: 10857763) Grant Information: N 121112600145-2) Saint-Petersburg State Research Institute of Phthisiopulmonology within the framework of the State task of the Ministry of Health of the Russian Federation; No SPARC/2019-2020/P2420/SL ministry of Education (MoE) Govt of India through the SPARC (Scheme for Promotion of Academic and Research Collaboration); Project No. INT/RUS/RFBR/380 Government of India under Indo-Russia cooperation program Contributed Indexing: Keywords: Anti-tuberculosis therapy; Extracellular vesicles; Mesenchymal stem cells; Proteins; Renal tuberculosis Substance Nomenclature: 0 (Cytokines) ; 0 (Anti-Inflammatory Agents) Entry Date(s): Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240227 Update Code: 20240227 PubMed Central ID: PMC10894196

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Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.