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

Abstract : 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
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https://www.hal.inserm.fr/inserm-02563336
Contributor : Bruna Lima Correa <>
Submitted on : Tuesday, May 5, 2020 - 11:42:33 AM
Last modification on : Thursday, May 7, 2020 - 1:41:12 AM

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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, Oxford University Press (OUP), 2020, pp.cvaa028. ⟨10.1093/cvr/cvaa028⟩. ⟨inserm-02563336⟩

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