We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFβ, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFβ, IL-10, and IL-1α concentrations.
Similar content being viewed by others
References
Andreeva ER, Buravkova LB. Multipotent mesenchymal stromal and immune cells interaction: reciprocal effects. Ross. Fiziol. Zh. 2012;98(12):1441-1459. Russian.
Mayanskaya IV, Goganova AYu, Tolkachova NI, Achkinazi VI, Mayansky AN. Immunosuppressive activity of mesenchymal stem (stromal) cells. Immunologiya. 2013;34(2):122-128. Russian.
Petrov VN, Konoplyannikov AG, Sayapina EV, Konoplyannikova OA, Lepekhina LA, Kal’sina SSh, Semenkova IV, Agaeva EV. In vitro modifying the effect of mesenchymal stem cells on production of reactive oxygen species by macrophagez in allogeneic and xenogeneic co-culturing systems. Autologous Stem Cells: Experimental Studies and Prospects of Clinical Application. Tkachuk VA, ed. Moscow, 2009. P. 429-448. Russian.
Tsyb AF, Konoplyannikov AG, Kaplan MA, Popovkina OE, Lepekhina LA, Kal’sina SSh, Semenkova IV, Agaeva EE, Danilenko AA. The use of systemic transplantation of “cardiomyoblasts” derived from autologous bone marrow mesenchymal stem cells in the complex therapy of patients with chronic heart failure. Geny Kletki. 2009;4(1):78-84. Russian.
Tsyb AF, Konoplyannikov AG, Kolesnikova AI, Pavlov VV. Preparation and clinical application of human bone marrow mesenchymal stem cell cultures. Vestn. Ross. Akad. Med. Nauk. 2004;(9):71-76. Russian.
Tsyb AF, Yuzhakov VV, Roshal’ LM, Sukhikh GT, Konoplyannikov AG, Sushkevich GN, Yakovleva ND, Ingel’ IE, Bandurko LN, Sevan’kaeva LE, Mikhina LN, Fomina NK, Marei MV, Semenova ZhB, Konoplyannikova OA, Kalsina SSh, Lepekhina LA, Semenkova IV, Agaeva EV, Shevchuk AS, Pavlova LN, Tokarev OY, Karaseva OV, Chernyshova TA. Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury. Bull. Exp. Biol. Med. 2009;147(1):132-146.
Schwartz YS, Svistelnik AV. Functional phenotypes of macrophages and the M1-M2 polarization concept. Part I. Proinflammatory phenotype. Biochemistry (Mosc.). 2012;77(3):246-260.
Astori G, Amati E, Bambi F, Bernardi M, Chieregato K, Schäfer R, Sella S, Rodeghiero F. Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future. Stem Cell Res Ther. 2016;7(1):93.
Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T. Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Cell Stem Cell. 2008;2(6):566-575.
Cassatella MA, Mosna F, Micheletti A, Lisi V, Tamassia N, Cont C, Calzetti F, Pelletier M, Pizzolo G, Krampera M. Tolllike receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells. 2011;29(6):1001-1011.
de Oliveira Bravo M, Carvalho JL, Saldanha-Araujo F. Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression. Purinergic Signal. 2016;12(4):595-609.
Fontaine MJ, Shih H, Schäfer R, Pittenger MF. Unraveling the mesenchymal stromal cells’ paracrine immunomodulatory effects. Transfus. Med. Rev. 2016;30(1):37-43.
Glenn JD, Whartenby KA. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy. World J. Stem Cells. 2014;6(5):526-539.
Gómez-Aristizábal A, Kim KP, Viswanathan S. A Systematic study of the effect of different molecular weights of hyaluronic acid on mesenchymal stromal cell-mediated immunomodulation. PLoS One. 2016;11(1):e0147868. doi: https://doi.org/10.1371/journal. pone.0147868.
Goodridge HS, Simmons RM, Underhill D.M. Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J. Immunol. 2007;178(5):3107-3115.
Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW, George R, Lardo A. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012;308(22):2369-2379.
Hoogduijn MJ, Crop MJ, Peeters AM, Korevaar SS, Eijken M, Drabbels JJ, Roelen DL, Maat AP, Balk AH, Weimar W, Baan CC. Donor-derived mesenchymal stem cells remain present and functional in transplanted human heart. Am. J. Transplant. 2009;9(1):222-230.
Jiang CY, Gui C, He AN, Hu XY, Chen J, Jiang Y, Wang JA. Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction. J. Zhejiang Univ Sci B. 2008;9(8):630-637.
Kelly EK, Wang L, Ivashkiv LB. Calcium-activated pathways and oxidative burst mediate zymosan-induced signaling and IL-10 production in human macrophages. J. Immunol. 2010;184(10):5545-5552.
Le Blanc K, Davies LC. Mesenchymal stromal cells and the innate immune response. Immunol. Lett. 2015;168(2):140-146.
Lee RH, Pulin A.A, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5(1):54-63.
Leibacher J, Henschler R. Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells. Stem Cell Res. Ther. 2016;7:7. doi: https://doi.org/10.1186/s13287-015-0271-2.
Lin YC, Leu S, Sun CK, Yen CH, Kao YH, Chang LT, Tsai TH, Chua S, Fu M, Ko SF, Wu CJ, Lee FY, Yip HK. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy. J. Transl. Med. 2010;8:88. doi: https://doi.org/10.1186/1479-5876-8-88.
Molina ER, Smith BT, Shah SR, Shin H, Mikos AG. Immunomodulatory properties of stem cells and bioactive molecules for tissue engineering. J. Contol. Release. 2015;219):107-118.
Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F, Ottonello L, Pistoia V. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells. 2008;26(1):151-162.
Selleri S, Bifsha P, Civini S, Pacelli C, Dieng M.M, Lemieux W, Jin P, Bazin R, Patey N, Marincola F.M, Moldovan F, Zaouter C, Trudeau L.E, Benabdhalla B, Louis I, Beauséjour C, Stroncek D, Le Deist F, Haddad E. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming. Oncotarget. 2016;7(21):30 193-30 210.
Sharma RR, Pollock K, Hubel A, McKenna D. Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion. 2014;54(5):1418-1437.
van den Akker F, de Jager S.C, Sluijter JP. Mesenchymal stem cell therapy for cardiac inflammation: immunomodulatory properties and the influence of toll-like receptors. Mediators Inflamm. 2013;2013. ID 181020. doi: https://doi.org/10.1155/2013/181020.
Zheng G, Ge M, Qiu G, Shu Q, Xu J. Mesenchymal stromal cells affect disease outcomes via macrophage polarization. Stem Cells Int. 2015;2015. ID 989473. doi: https://doi.org/10.1155/2015/989473.
Zimmermann JA, Hettiaratchi M.H, McDevitt T.C. Enhanced immunosuppression of T cells by sustained presentation of bioactive interferon-γ within three-dimensional mesenchymal stem cell constructs. Stem Cells Transl. Med. 2017;6(1):223-237.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 139-147, July, 2017
Rights and permissions
About this article
Cite this article
Petrov, V.N., Agaeva, E.V., Popovkina, O.E. et al. Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure. Bull Exp Biol Med 164, 233–240 (2017). https://doi.org/10.1007/s10517-017-3965-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-017-3965-x