INNATE-MI
Project's code: PN-III-P4-ID-PCCF-2016-0172
Project's title: Targeting innate immune mechanisms to improve risk stratification and to identify future therapeutic options in myocardial infarction
Contract number: 05/18.07.2018
Coordinator: Acad.Maya Simionescu
Research Partners:
CO: Institute of Cellular Biology and Pathology "Nicolae Simionescu", BUCHAREST
P1: University of Medicine, Pharmacy, Science and Technology, TARGU MURES
P2: University of Medicine and Pharmacy "Carol Davila" BUCHAREST
Budget: 8.500.000 Lei
Period: 18.07.2018 – 31.06.2022
Project Summary:
Myocardial infarction (MI) is a major cause of morbidity and mortality. At present, clinicians lack specific biomarkers for accurate post-MI risk stratification and therapeutic tools to modulate myocardial inflammation and to promote efficient recovery. Innate immune processes mediated by polymorphonuclear neutrophils (PMN) and macrophages (MAC) in the immediate post-MI period determine the extent of myocardial damage but also induce repair. Our major goal is to identify central molecules that mediate the crosstalk between sub-populations of PMN and MAC, and determine their involvement in MI. Additionally, we will test the ability of specific therapies to regulate myocardial inflammation and to improve cardiac function in-vivo. Project objectives are: (1) To identify key mediators that determine post-MI myocardial remodeling and prognosis – We will investigate the relationships between the soluble PMN/MAC mediators, post-MI cardiac function and prognosis in MI patients; (2) Investigation of the crosstalk between PMN and MAC in MI – We will use in-vitro studies, genomics and proteomics to identify mediators that govern the PMN-induced MAC polarization into sub-populations that promote repair. The role of the identified molecules will be tested in-vivo; (3) Development of a mesenchymal stem cell (MSC)-based therapy in MI – We will investigate the ability of MSC treatment to shift PMN and MAC polarization towards reparatory phenotypes, and to improve cardiac recovery; (4) To investigate S100A8/A9 blockade as potential therapy in MI – S100A8/A9 is a potent pro-inflammatory molecule secreted by PMN and MAC. We will assess whether S100A8/A9 blockade inhibits inflammation and improves post-MI cardiac function. The expected outcome is to identify biomarkers that can be used to accurately identify patients at high risk to suffer new events. MSC therapy or S100A8/A9 blockade might improve recovery of MI patients and reduce morbidity and mortality in this large patient group.
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Our laboratoy is involved in objective 3: Exploiting the immuno-modulatory properties of MSC to reduce inflammation and promote myocardial recovery post-MI (cell therapy)
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Dissemination of results
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Publications:
1. Preda MB et al. Evidence of mesenchymal stromal cell adaptation to local microenvironment following subcutaneous transplantation. J Cell Mol Med 2020; 24(18):10889-10897. (IF. 5.310)
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2. Popescu et al. Dual Stem Cell Therapy Improves the Myocardial Recovery Post-Infarction through Reciprocal Modulation of Cell Functions. Int J Mol Sci. 2021 May 26;22(11):5631. (IF. 5.923)
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Presentations at international scientific conferences:
1. M.B. Preda, S. Popescu, R. Tutuianu, A.M. Rosca, M. Simionescu, A. Burlacu. Hypoxia regulates the pro-angiogenic effect of subcutaneously transplanted mesenchymal stromal cells. Keystone Symposia meeting on Therapeutic Targeting of Hypoxia-Sensitive Pathways. 10-14.04.2018. University of Oxford Mathematical Institute, Oxford, UK (poster).
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2. S Popescu, A.M. Lupan, M.B. Preda, A. Burlacu, M. Simionescu. Cross-talk between mesenchymal stromal cells and endothelial progenitors modulates the expression of angiogenesis related molecules. 06-09.07.2018. The 36th Annual Scientific Session of the Romanian Society for Cell Biology and the 10th National Congress with International participation, Craiova, Romania. (oral presentation).
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3. M.B. Preda, S. Popescu, R. Tutuianu, A.M. Rosca, M. Simionescu, A. Burlacu. Hypoxia regulates the pro-angiogenic effect of subcutaneously transplanted mesenchymal stromal cells. EMBO Conference: The Molecular and Cellular Basis of Regeneration and Tissue Repair. 15-19 September 2018. Valetta, Malta (poster).