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
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
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.
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)
Dissemination of results
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)
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)
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).
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).
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).