Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.
Anti-tuberculosis therapy
Extracellular vesicles
Mesenchymal stem cells
Proteins
Renal tuberculosis
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 Feb 2024
24 Feb 2024
Historique:
received:
11
11
2023
accepted:
19
02
2024
medline:
25
2
2024
pubmed:
25
2
2024
entrez:
24
2
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38402260
doi: 10.1038/s41598-024-54992-z
pii: 10.1038/s41598-024-54992-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4495Subventions
Organisme : Saint-Petersburg State Research Institute of Phthisiopulmonology within the framework of the State task of the Ministry of Health of the Russian Federation
ID : N 121112600145-2)
Organisme : ministry of Education (MoE) Govt of India through the SPARC (Scheme for Promotion of Academic and Research Collaboration)
ID : No SPARC/2019-2020/P2420/SL
Organisme : Government of India under Indo-Russia cooperation program
ID : Project No. INT/RUS/RFBR/380
Informations de copyright
© 2024. The Author(s).
Références
Bagcchi, S. WHO’s global tuberculosis report 2022. Lancet Microbe 4(1), e20 (2023).
pubmed: 36521512
doi: 10.1016/S2666-5247(22)00359-7
Hutchings, M. I., Truman, A. W. & Wilkinson, B. Antibiotics: Past, present and future. Curr. Opin. Microbiol. 51, 72–80 (2019).
pubmed: 31733401
doi: 10.1016/j.mib.2019.10.008
Leise, M. D., Poterucha, J. J. & Talwalkar, J. A. Drug-induced liver injury. Mayo Clin. Proc. 89(1), 95–106 (2014).
pubmed: 24388027
doi: 10.1016/j.mayocp.2013.09.016
Shamputa, I. C. et al. Endogenous reactivation and true treatment failure as causes of recurrent tuberculosis in a high incidence setting with a low HIV infection. Trop. Med. Int. Health 12(6), 700–708 (2007).
pubmed: 17550467
doi: 10.1111/j.1365-3156.2007.01840.x
Ramappa, V. & Aithal, G. P. Hepatotoxicity related to anti-tuberculosis drugs: Mechanisms and management. J. Clin. Exp. Hepatol. 3(1), 37–49 (2013).
pubmed: 25755470
doi: 10.1016/j.jceh.2012.12.001
Kumar, R. et al. Antituberculosis therapy-induced acute liver failure: Magnitude, profile, prognosis, and predictors of outcome. Hepatology 51(5), 1665–1674 (2010).
pubmed: 20196116
doi: 10.1002/hep.23534
Yan, K., Xu, G. & Li, Z. MicroRNA-20b carried by mesenchymal stem cell-derived extracellular vesicles protects alveolar epithelial type II cells from Mycobacterium tuberculosis infection in vitro. Infect. Genet. Evol. 101, 105292 (2022).
pubmed: 35504589
doi: 10.1016/j.meegid.2022.105292
Yudintceva, N. et al. Mesenchymal stem cells and MSCs-derived extracellular vesicles in infectious diseases: From basic research to clinical practice. Bioengineering (Basel) 9(11), 662 (2022).
pubmed: 36354573
doi: 10.3390/bioengineering9110662
Caplan, A. I. & Dennis, J. E. Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5), 1076–1084 (2006).
pubmed: 16619257
doi: 10.1002/jcb.20886
De Jong, O. G. et al. Extracellular vesicles: Potential roles in regenerative medicine. Front. Immunol. 5, 608 (2014).
pubmed: 25520717
pmcid: 4253973
Elahi, F. M. et al. Preclinical translation of exosomes derived from mesenchymal stem/stromal cells. Stem Cells 38(1), 15–21 (2020).
pubmed: 31381842
doi: 10.1002/stem.3061
Börger, V. et al. Mesenchymal stem/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents. Int. J. Mol. Sci. 18(7), 1450 (2017).
pubmed: 28684664
pmcid: 5535941
doi: 10.3390/ijms18071450
Lou, G. et al. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp. Mol. Med. 49(6), e346 (2017).
pubmed: 28620221
pmcid: 5519012
doi: 10.1038/emm.2017.63
Murphy, D. E. et al. Extracellular vesicle-based therapeutics: Natural versus engineered targeting and trafficking. Exp. Mol. Med. 51(3), 1–12 (2019).
pubmed: 30872574
doi: 10.1038/s12276-019-0223-5
Kooijmans, S. A. A. et al. Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: New nanotools for cancer treatment. Pharmacol. Res. 111, 487–500 (2016).
pubmed: 27394168
doi: 10.1016/j.phrs.2016.07.006
Xu, F. et al. Mesenchymal stem cell-derived extracellular vesicles with high PD-L1 expression for autoimmune diseases treatment. Adv. Mater. 34(1), e2106265 (2022).
pubmed: 34613627
doi: 10.1002/adma.202106265
Chow, L. et al. Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells. Stem Cells Transl. Med. 9(2), 235–249 (2020).
pubmed: 31702119
doi: 10.1002/sctm.19-0092
Harman, R. M. et al. Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds. Stem Cell Res. Ther. 8(1), 157 (2017).
pubmed: 28676123
pmcid: 5496374
doi: 10.1186/s13287-017-0610-6
Sutton, M. T. et al. Antimicrobial properties of mesenchymal stem cells: Therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int. 2016, 5303048 (2016).
pubmed: 26925108
pmcid: 4746399
doi: 10.1155/2016/5303048
Zhang, X. et al. Mesenchymal stem cells and tuberculosis: Clinical challenges and opportunities. Front. Immunol. 12, 695278 (2021).
pubmed: 34367155
pmcid: 8340780
doi: 10.3389/fimmu.2021.695278
Li, P., Zhao, Y. & Ge, L. Therapeutic effects of human gingiva-derived mesenchymal stromal cells on murine contact hypersensitivity via prostaglandin E2-EP3 signaling. Stem Cell Res. Ther. 7(1), 103 (2016).
pubmed: 27484807
pmcid: 4969691
doi: 10.1186/s13287-016-0361-9
Colombo, M., Raposo, G. & Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30, 255–289 (2014).
pubmed: 25288114
doi: 10.1146/annurev-cellbio-101512-122326
Favaro, E. et al. Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes. Diabetologia 57(8), 1664–1673 (2014).
pubmed: 24838680
doi: 10.1007/s00125-014-3262-4
Ren, W. et al. Extracellular vesicles secreted by hypoxia pre-challenged mesenchymal stem cells promote non-small cell lung cancer cell growth and mobility as well as macrophage M2 polarization via miR-21-5p delivery. J. Exp. Clin. Cancer Res. 38(1), 62 (2019).
pubmed: 30736829
pmcid: 6367822
doi: 10.1186/s13046-019-1027-0
Zhang, X. et al. Human gingiva-derived mesenchymal stem cells modulate monocytes/macrophages and alleviate atherosclerosis. Front. Immunol. 9, 878 (2018).
pubmed: 29760701
pmcid: 5937358
doi: 10.3389/fimmu.2018.00878
Nassar, W. et al. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res. 20, 21 (2016).
pubmed: 27499886
pmcid: 4974791
doi: 10.1186/s40824-016-0068-0
Mokarizadeh, A. et al. Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling. Immunol. Lett. 147(1–2), 47–54 (2012).
pubmed: 22705267
doi: 10.1016/j.imlet.2012.06.001
Yudintceva, N. M. et al. Application of the allogenic mesenchymal stem cells in the therapy of the bladder tuberculosis. J. Tissue Eng. Regen. Med. 12(3), e1580–e1593 (2018).
pubmed: 28990734
doi: 10.1002/term.2583
Cantaluppi, V. et al. Rationale of mesenchymal stem cell therapy in kidney injury. Am. J. Kidney Dis. 61(2), 300–309 (2013).
pubmed: 22938846
doi: 10.1053/j.ajkd.2012.05.027
Grange, C. et al. Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy. Sci. Rep. 9(1), 4468 (2019).
pubmed: 30872726
pmcid: 6418239
doi: 10.1038/s41598-019-41100-9
Bruno, S. et al. Role of extracellular vesicles in stem cell biology. Am. J. Physiol. Cell Physiol. 317(2), C303-c313 (2019).
pubmed: 31091143
pmcid: 6732418
doi: 10.1152/ajpcell.00129.2019
Collino, F. et al. AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying MicroRNAs. J. Am. Soc. Nephrol. 26(10), 2349–2360 (2015).
pubmed: 25901032
pmcid: 4587694
doi: 10.1681/ASN.2014070710
Nimiritsky, P. P. et al. Unveiling mesenchymal stromal cells’ organizing function in regeneration. Int. J. Mol. Sci. 20(4), 823 (2019).
pubmed: 30769851
pmcid: 6413004
doi: 10.3390/ijms20040823
Shi, Y. et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat. Rev. Nephrol. 14(8), 493–507 (2018).
pubmed: 29895977
doi: 10.1038/s41581-018-0023-5
Bin, A. et al. The ecto-enzymes CD73 and adenosine deaminase modulate 5′-AMP-derived adenosine in myofibroblasts of the rat small intestine. Purinergic Signal 14(4), 409–421 (2018).
pubmed: 30269308
pmcid: 6298927
doi: 10.1007/s11302-018-9623-6
Bentala, H. et al. Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. Shock 18(6), 561–566 (2002).
pubmed: 12462566
doi: 10.1097/00024382-200212000-00013
Khundmiri, S. J. et al. Effect of reversible and irreversible ischemia on marker enzymes of BBM from renal cortical PT subpopulations. Am. J. Physiol. 273(6), F849–F856 (1997).
pubmed: 9435672
Zhu, X. & Hu, J. Adenosine deaminase is a potential molecular marker for diagnosis and prognosis of haemorrhagic fever with renal syndrome. Infect. Drug Resist. 15, 5197–5205 (2022).
pubmed: 36090607
pmcid: 9462936
doi: 10.2147/IDR.S379228
Vallon, V., Mühlbauer, B. & Osswald, H. Adenosine and kidney function. Physiol. Rev. 86(3), 901–940 (2006).
pubmed: 16816141
doi: 10.1152/physrev.00031.2005
Kim, J. Y. et al. Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection. J. Infect. 77(4), 314–320 (2018).
pubmed: 29746954
doi: 10.1016/j.jinf.2018.04.011
Roberts, V. S. et al. The role of adenosine receptors A2A and A2B signaling in renal fibrosis. Kidney Int. 86(4), 685–692 (2014).
pubmed: 25054776
doi: 10.1038/ki.2014.244
Hochepied, T. et al. Alpha(1)-acid glycoprotein: An acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev. 14(1), 25–34 (2003).
pubmed: 12485617
doi: 10.1016/S1359-6101(02)00054-0
Huang, Q. et al. Extracellular vesicle-packaged ILK from mesothelial cells promotes fibroblast activation in peritoneal fibrosis. J. Extracell. Vesicles 12(7), e12334 (2023).
pubmed: 37357686
doi: 10.1002/jev2.12334
Junttila, I. S. Tuning the cytokine responses: An update on interleukin (IL)-4 and IL-13 receptor complexes. Front. Immunol. 9, 888 (2018).
pubmed: 29930549
pmcid: 6001902
doi: 10.3389/fimmu.2018.00888
Labuz, D. et al. Interleukin-4 induces the release of opioid peptides from M1 macrophages in pathological pain. J. Neurosci. 41(13), 2870–2882 (2021).
pubmed: 33593854
pmcid: 8018889
doi: 10.1523/JNEUROSCI.3040-20.2021
Kaufmann, S. H. How can immunology contribute to the control of tuberculosis?. Nat. Rev. Immunol. 1(1), 20–30 (2001).
pubmed: 11905811
doi: 10.1038/35095558
Saraiva, M. & O’Garra, A. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 10(3), 170–181 (2010).
pubmed: 20154735
doi: 10.1038/nri2711
Shaw, T. C., Thomas, L. H. & Friedland, J. S. Regulation of IL-10 secretion after phagocytosis of Mycobacterium tuberculosis by human monocytic cells. Cytokine 12(5), 483–486 (2000).
pubmed: 10857763
doi: 10.1006/cyto.1999.0586
Geginat, J. et al. The light and the dark sides of Interleukin-10 in immune-mediated diseases and cancer. Cytokine Growth Factor Rev. 30, 87–93 (2016).
pubmed: 26980675
doi: 10.1016/j.cytogfr.2016.02.003
Hao, L. et al. Lactoferrin: Major physiological functions and applications. Curr. Protein Pept. Sci. 20(2), 139–144 (2019).
pubmed: 29756573
doi: 10.2174/1389203719666180514150921
Perretti, M. & Dalli, J. Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics. Br. J. Pharmacol. 158(4), 936–946 (2009).
pubmed: 19845684
pmcid: 2785517
doi: 10.1111/j.1476-5381.2009.00483.x
Harrell, C. R. et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells 8(12), 1605 (2019).
pubmed: 31835680
pmcid: 6952783
doi: 10.3390/cells8121605
Luan, X. et al. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol. Sin. 38(6), 754–763 (2017).
pubmed: 28392567
pmcid: 5520184
doi: 10.1038/aps.2017.12
Zhou, Y. et al. The immunomodulatory functions of mesenchymal stromal/stem cells mediated via paracrine activity. J. Clin. Med. 8(7), 1025 (2019).
pubmed: 31336889
pmcid: 6678920
doi: 10.3390/jcm8071025
Muraviov, A. N. et al. The use of mesenchymal stem cells in the complex treatment of kidney tuberculosis (experimental study). Biomedicines 10(12), 3062 (2022).
pubmed: 36551818
pmcid: 9775022
doi: 10.3390/biomedicines10123062
Dominici, M. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8(4), 315–317t (2006).
pubmed: 16923606
doi: 10.1080/14653240600855905
Zhou, Y. et al. Injectable extracellular vesicle-released self-assembling peptide nanofiber hydrogel as an enhanced cell-free therapy for tissue regeneration. J. Control Release 316, 93–104 (2019).
pubmed: 31704110
doi: 10.1016/j.jconrel.2019.11.003
Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976).
pubmed: 942051
doi: 10.1016/0003-2697(76)90527-3
Laemmli, U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259), 680–685 (1970).
pubmed: 5432063
doi: 10.1038/227680a0
Towbin, H., Staehelin, T. & Gordon, J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc. Natl. Acad. Sci. U. S. A. 76(9), 4350–4354 (1979).
pubmed: 388439
pmcid: 411572
doi: 10.1073/pnas.76.9.4350
Ma, B. et al. PEAKS: Powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid Commun. Mass Spectrom. 17(20), 2337–2342 (2003).
pubmed: 14558135
doi: 10.1002/rcm.1196
Szklarczyk, D. et al. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49(D1), D605-d612 (2021).
pubmed: 33237311
doi: 10.1093/nar/gkaa1074
Spirin, V. & Mirny, L. A. Protein complexes and functional modules in molecular networks. Proc. Natl. Acad. Sci. U. S. A. 100(21), 12123–12128 (2003).
pubmed: 14517352
pmcid: 218723
doi: 10.1073/pnas.2032324100
Wang, J. et al. Recent advances in clustering methods for protein interaction networks. BMC Genom. 11(Suppl 3), S10 (2010).
doi: 10.1186/1471-2164-11-S3-S10
Visser, L. & Blout, E. R. The use of p-nitrophenyl N-tert-butyloxycarbonyl-L-alaninate as substrate for elastase. Biochim. Biophys. Acta 268(1), 257–260 (1972).
pubmed: 5062949
doi: 10.1016/0005-2744(72)90223-9
Bankhead, P. et al. QuPath: Open source software for digital pathology image analysis. Sci. Rep. 7(1), 16878 (2017).
pubmed: 29203879
pmcid: 5715110
doi: 10.1038/s41598-017-17204-5