Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

Bruna Lima Correa (1) , Nadia El Harane (1) , Ingrid Gomez (1) , Hocine Rachid Hocine (2) , José Vilar (1) , Manon Desgres (1) , Valérie Bellamy (1) , Kamaleswaran Keirththana (1) , Chloé Guillas (1) , Maria Perotto (1) , Laetitia Pidial (1) , Paul Alayrac (1) , Thi Tran (1) , Sisareuth Tan (3) , Thomas Hamada (1) , Dominique Charron (4) , Alain Brisson (3) , Nisa Renault (1, 5) , Reem Al-Daccak (4) , Philippe Menasché (1) , Jean-Sébastien Silvestre (1, 6)

1 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
2 Institut Curie [Paris]
3 CBMN - Chimie et Biologie des Membranes et des Nanoobjets
4 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
5 Fujifilm Cellular Dynamics Inc [Madison, WI, USA]
6 Service de Chirurgie Cardiovasculaire [Hôpital Européen Georges Pompidou - APHP]

The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In

Domaines: Biotechnologies

Bruna Lima Correa, Nadia El Harane, Ingrid Gomez, Hocine Rachid Hocine, José Vilar, et al.. Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts. Cardiovascular Research, 2020, pp.cvaa028. ⟨10.1093/cvr/cvaa028⟩. ⟨inserm-02563336⟩