Characteristics of the effect of exosomes isolated from donor plasma and placenta-derived mesenchymal stromal cell-conditioned medium on the paracrine secretion of human peripheral blood mononuclear cells
DOI:
https://doi.org/10.14739/2310-1210.2022.4.251058Keywords:
exosomes, chronic heart failure, placental mesenchymal stromal cells, VEGF-A, MCP-1, ICAM-1Abstract
Extracellular small vesicles – exosomes, attract the attention of researchers as a promising tool for regulating intercellular communication. At the same time, the therapeutic effects achieved through the use of mesenchymal stem cells (MSCs) are traditionally considered by medicine as a time-tested, multi-vector strategy for the treatment of various pathologies. In particular, in addition to the application of MSCs directly, it is important to study the products of their secretion.
Aim. To study characteristics of the influence of exosomes isolated from blood plasma of healthy donors and conditioned medium of placental mesenchymal stromal cell (MSC) culture on paracrine secretion of peripheral blood mononuclear cells (PBMCs) in patients with chronic heart failure (CHF) in vitro.
Materials and methods. The characteristics of paracrine secretion of PBMCs in patients with CHF by the content of proteins VEGF-A, MCP-1, ICAM-1 in their culture medium were studied in two directions: under the influence of exosomes isolated from plasma of healthy donors and exosomes isolated from placental MSC culture medium.
Results. Incubation of PBMCs with plasma exosomes increased VEGF-A secretion in the group of healthy donors by 2.73 times (P ≤ 0.05), in patients with CHF – by 2 times (P ≤ 0.05); but there were a multidirectional effect on the content of ICAM-1 protein: it was 1.8 times (P ≤ 0.05) increased in the group of donors and 1.4 times (P ≤ 0.05) decreased in the group of CHF patients; MCP-1 secretion was insignificantly 10 % reduced in the donor group and did not change significantly in patients. Incubation of РВМС with exosomes isolated from MSC conditioned medium did not cause significant changes in paracrine secretion of PBMCs: there was a decrease in secretion of VEGF-A by 25 %, ICAM-1 by 17 %, MCP-1 by 22 % in the group of healthy volunteers; secretion of these proteins was 19.7 %, 22.0 % and 25.0 % decreased, respectively, in the group of CHF patients. The effects observed in the incubation of PBMCs with exosomes isolated from blood plasma of healthy donors and conditioned medium of placental MSC culture have provided valuable information for the design of future studies in this area of cell biology.
Conclusions. Our studies have demonstrated in vitro the effects of exosomes isolated from donor plasma and conditioned medium on the functional properties of human PBMCs.
References
Inamdar, A. A., & Inamdar, A. C. (2016). Heart Failure: Diagnosis, Management and Utilization. Journal of clinical medicine, 5(7), 62. https://doi.org/10.3390/jcm5070062
Bernardi, S., & Balbi, C. (2020). Extracellular Vesicles: From Biomarkers to Therapeutic Tools. Biology, 9(9), 258. https://doi.org/10.3390/biology9090258
van Niel, G., D'Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature reviews. Molecular cell biology, 19(4), 213-228. https://doi.org/10.1038/nrm.2017.125
Wang, A. (2021). Human Induced Pluripotent Stem Cell-Derived Exosomes as a New Therapeutic Strategy for Various Diseases. International journal of molecular sciences, 22(4), 1769. https://doi.org/10.3390/ijms22041769
Fan, X. L., Zhang, Y., Li, X., & Fu, Q. L. (2020). Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cellular and molecular life sciences : CMLS, 77(14), 2771-2794. https://doi.org/10.1007/s00018-020-03454-6
Planat-Benard, V., Varin, A., & Casteilla, L. (2021). MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism. Frontiers in immunology, 12, 626755. https://doi.org/10.3389/fimmu.2021.626755
Rani, S., Ryan, A. E., Griffin, M. D., & Ritter, T. (2015). Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Molecular therapy, 23(5), 812-823. https://doi.org/10.1038/mt.2015.44
Yin, K., Wang, S., & Zhao, R. C. (2019). Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm. Biomarker research, 7, 8. https://doi.org/10.1186/s40364-019-0159-x
Jafarinia, M., Alsahebfosoul, F., Salehi, H., Eskandari, N., & Ganjalikhani-Hakemi, M. (2020). Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy. Immunological investigations, 49(7), 758-780. https://doi.org/10.1080/08820139.2020.1712416
Varderidou-Minasian, S., & Lorenowicz, M. J. (2020). Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics, 10(13), 5979-5997. https://doi.org/10.7150/thno.40122
Natrus, L. V., Muzychenko, P. F., Labudzynskyi, D. O., Chernovol, P. A., & Klys, Y. G. (2020). Plasma exosomes impact on paracrine secretion of peripheral blood mononuclear cells in patients with chronic heart failure. Fiziologichnyi Zhurnal, 66(6), 21-32. https://doi.org/10.15407/fz66.06.021
Riedhammer, C., Halbritter, D., & Weissert, R. (2016). Peripheral Blood Mononuclear Cells: Isolation, Freezing, Thawing, and Culture. Methods in molecular biology (Clifton, N.J.), 1304, 53–61. https://doi.org/10.1007/7651_2014_99
Shablii, V., Kuchma, M., Svitina, H., Skrypkina, I., Areshkov, P., Kyryk, V., Bukreieva, T., Nikulina, V., Shablii, I., & Lobyntseva, G. (2019). High Proliferative Placenta-Derived Multipotent Cells Express Cytokeratin 7 at Low Level. BioMed research international, 2019, 2098749. https://doi.org/10.1155/2019/2098749
Patel, G. K., Khan, M. A., Zubair, H., Srivastava, S. K., Khushman, M., Singh, S., & Singh, A. P. (2019). Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Scientific reports, 9(1), 5335. https://doi.org/10.1038/s41598-019-41800-2
Pannella, M., Caliceti, C., Fortini, F., Aquila, G., Vieceli Dalla Sega, F., Pannuti, A., Fortini, C., Morelli, M. B., Fucili, A., Francolini, G., Voltan, R., Secchiero, P., Dinelli, G., Leoncini, E., Ferracin, M., Hrelia, S., Miele, L., & Rizzo, P. (2016). Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells. Journal of cellular physiology, 231(12), 2700-2710. https://doi.org/10.1002/jcp.25373
Khurana, R., Simons, M., Martin, J. F., & Zachary, I. C. (2005). Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation, 112(12), 1813-1824. https://doi.org/10.1161/CIRCULATIONAHA.105.535294
Xu, X. H., Xu, J., Xue, L., Cao, H. L., Liu, X., & Chen, Y. J. (2011). VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation. Journal of cardiothoracic surgery, 6, 54. https://doi.org/10.1186/1749-8090-6-54
Favaloro, L., Diez, M., Mendiz, O., Janavel, G. V., Valdivieso, L., Ratto, R., Garelli, G., Salmo, F., Criscuolo, M., Bercovich, A., & Crottogini, A. (2013). High-dose plasmid-mediated VEGF gene transfer is safe in patients with severe ischemic heart disease (Genesis-I). A phase I, open-label, two-year follow-up trial. Catheterization and cardiovascular interventions, 82(6), 899-906. https://doi.org/10.1002/ccd.24555
Kukuła, K., Chojnowska, L., Dąbrowski, M., Witkowski, A., Chmielak, Z., Skwarek, M., Kądziela, J., Teresińska, A., Małecki, M., Janik, P., Lewandowski, Z., Kłopotowski, M., Wnuk, J., & Rużyłło, W. (2011). Intramyocardial plasmid-encoding human vascular endothelial growth factor A165/basic fibroblast growth factor therapy using percutaneous transcatheter approach in patients with refractory coronary artery disease (VIF-CAD). American heart journal, 161(3), 581-589. https://doi.org/10.1016/j.ahj.2010.11.023
Jaipersad, A. S., Lip, G. Y., Silverman, S., & Shantsila, E. (2014). The role of monocytes in angiogenesis and atherosclerosis. Journal of the American College of Cardiology, 63(1), 1-11. https://doi.org/10.1016/j.jacc.2013.09.019
Bouwens, E., van den Berg, V. J., Akkerhuis, K. M., Baart, S. J., Caliskan, K., Brugts, J. J., Mouthaan, H., Ramshorst, J. V., Germans, T., Umans, V., Boersma, E., & Kardys, I. (2020). Circulating Biomarkers of Cell Adhesion Predict Clinical Outcome in Patients with Chronic Heart Failure. Journal of clinical medicine, 9(1), 195. https://doi.org/10.3390/jcm9010195
Lin, Q. Y., Lang, P. P., Zhang, Y. L., Yang, X. L., Xia, Y. L., Bai, J., & Li, H. H. (2019). Pharmacological blockage of ICAM-1 improves angiotensin II-induced cardiac remodeling by inhibiting adhesion of LFA-1+ monocytes. American journal of physiology. Heart and circulatory physiology, 317(6), H1301-H1311. https://doi.org/10.1152/ajpheart.00566.2019
Bui, T. M., Wiesolek, H. L., & Sumagin, R. (2020). ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. Journal of leukocyte biology, 108(3), 787-799. https://doi.org/10.1002/JLB.2MR0220-549R
Morimoto, H., & Takahashi, M. (2007). Role of monocyte chemoattractant protein-1 in myocardial infarction. International journal of biomedical science : IJBS, 3(3), 159-167.
Morimoto, H., Takahashi, M., Izawa, A., Ise, H., Hongo, M., Kolattukudy, P. E., & Ikeda, U. (2006). Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice prevents cardiac dysfunction and remodeling after myocardial infarction. Circulation research, 99(8), 891-899. https://doi.org/10.1161/01.RES.0000246113.82111.2d
Bianconi, V., Sahebkar, A., Atkin, S. L., & Pirro, M. (2018). The regulation and importance of monocyte chemoattractant protein-1. Current opinion in hematology, 25(1), 44-51. https://doi.org/10.1097/MOH.0000000000000389
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