Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Oct 21

PMID 27764217

Citations 23

Authors

Al Shaimaa Hasan

Lan Luo

Chen Yan

Tian-Xia Zhang

Yoshishige Urata

Shinji Goto

Safwat A Mangoura

Mahmoud H Abdel-Raheem

Shouhua Zhang

Tao-Sheng Li

Affiliations

Soon will be listed here.

Abstract

Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.

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References

Wu J, Li J, Zhang N, Zhang C . Stem cell-based therapies in ischemic heart diseases: a focus on aspects of microcirculation and inflammation. Basic Res Cardiol. 2011; 106(3):317-24. PMC: 3143577. DOI: 10.1007/s00395-011-0168-x. View

Takeuch O, Akira S . Epigenetic control of macrophage polarization. Eur J Immunol. 2011; 41(9):2490-3. DOI: 10.1002/eji.201141792. View

Sica A, Mantovani A . Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012; 122(3):787-95. PMC: 3287223. DOI: 10.1172/JCI59643. View

Ben-Mordechai T, Holbova R, Landa-Rouben N, Harel-Adar T, Feinberg M, Abd Elrahman I . Macrophage subpopulations are essential for infarct repair with and without stem cell therapy. J Am Coll Cardiol. 2013; 62(20):1890-901. DOI: 10.1016/j.jacc.2013.07.057. View

Zhang Q, Su W, Shi S, Wilder-Smith P, Xiang A, Wong A . Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells. 2010; 28(10):1856-68. PMC: 3114043. DOI: 10.1002/stem.503. View

Francois M, Romieu-Mourez R, Li M, Galipeau J . Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther. 2011; 20(1):187-95. DOI: 10.1038/mt.2011.189. View

Aminzadeh M, Tseliou E, Sun B, Cheng K, Malliaras K, Makkar R . Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy. Eur Heart J. 2014; 36(12):751-62. PMC: 4368856. DOI: 10.1093/eurheartj/ehu196. View

Dayan V, Yannarelli G, Billia F, Filomeno P, Wang X, Davies J . Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction. Basic Res Cardiol. 2011; 106(6):1299-310. DOI: 10.1007/s00395-011-0221-9. View

Lee S, White A, Matsushita S, Malliaras K, Steenbergen C, Zhang Y . Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction. J Am Coll Cardiol. 2011; 57(4):455-65. DOI: 10.1016/j.jacc.2010.07.049. View

10.

Nahrendorf M, Swirski F . Monocyte and macrophage heterogeneity in the heart. Circ Res. 2013; 112(12):1624-33. PMC: 3753681. DOI: 10.1161/CIRCRESAHA.113.300890. View

11.

Lee R, Pulin A, Seo M, Kota D, Ylostalo J, Larson B . 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. PMC: 4154377. DOI: 10.1016/j.stem.2009.05.003. View

12.

Gordon S, Taylor P . Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005; 5(12):953-64. DOI: 10.1038/nri1733. View

13.

Gordon S, Martinez F . Alternative activation of macrophages: mechanism and functions. Immunity. 2010; 32(5):593-604. DOI: 10.1016/j.immuni.2010.05.007. View

14.

Chimenti I, Ruckdeschel Smith R, Li T, Gerstenblith G, Messina E, Giacomello A . Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010; 106(5):971-80. PMC: 4317351. DOI: 10.1161/CIRCRESAHA.109.210682. View

15.

Ertl G, Frantz S . Healing after myocardial infarction. Cardiovasc Res. 2005; 66(1):22-32. DOI: 10.1016/j.cardiores.2005.01.011. View

16.

Mantovani A, Biswas S, Galdiero M, Sica A, Locati M . Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2012; 229(2):176-85. DOI: 10.1002/path.4133. View

17.

Malliaras K, Li T, Luthringer D, Terrovitis J, Cheng K, Chakravarty T . Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation. 2011; 125(1):100-12. PMC: 3256094. DOI: 10.1161/CIRCULATIONAHA.111.042598. View

18.

Malliaras K, Makkar R, Smith R, Cheng K, Wu E, Bonow R . Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol. 2013; 63(2):110-22. PMC: 3947063. DOI: 10.1016/j.jacc.2013.08.724. View

19.

Makkar R, Smith R, Cheng K, Malliaras K, Thomson L, Berman D . Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012; 379(9819):895-904. PMC: 4326004. DOI: 10.1016/S0140-6736(12)60195-0. View

20.

Hu Y, Zhang H, Lu Y, Bai H, Xu Y, Zhu X . Class A scavenger receptor attenuates myocardial infarction-induced cardiomyocyte necrosis through suppressing M1 macrophage subset polarization. Basic Res Cardiol. 2011; 106(6):1311-28. DOI: 10.1007/s00395-011-0204-x. View