Details

Autor(en) / Beteiligte

• El harane, Nadia
• Rachid, Hocine
• Gomez, Ingrid
• Lima Correa, Bruna
• Vilar, Jose
• Bellamy, Valérie
• Pidial, Laetitita
• Desgres, Manon
• Alayrac, Paul
• Charron, Dominique
• Renault, Nisa
• Al-Daccak, Reem
• Silvestre, Jean-Sébastien
• Menasché, Philippe

Titel

Abstract 10892: Induced Pluripotent Stem Cell-Derived Extracellular Vesicles May Not Trigger an Immune Response

Ist Teil von

• Circulation (New York, N.Y.), 2018-11, Vol.138 (Suppl_1 Suppl 1), p.A10892-A10892

Ort / Verlag

by the American College of Cardiology Foundation and the American Heart Association, Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• IntroductionExtracellular vesicles (EV) recapitulate most of the cardioprotective effects of their parent cells but their immunological behavior, a critical determinant of their clinical translatability, still remains unsettled.HypothesisEV from allogeneic induced pluripotent stem cells (iPSC)-derived cardiovascular progenitor (Pg) cells may not trigger an immune response.MethodsEV from cardiovascular Pg cells (differentiated from human iPSC) were first assessed in vitro for the expression of immune-relevant and stem cell markers by flow cytometry and their cross-talk with allogeneic T and NK cells (collected from healthy donors) was determined by tailored-immune assays. Next, immunocompetent mice underwent myocardial infarction by permament coronary artery ligation and the surviving mice received transcutaneous echo-guided intra-myocardial injections of EV or PBS at 2 days (n=6 per group) or EV, hiPSC-Pg or PBS at 3 weeks (n= 6-7 per group) after infarction. Cardiac and systemic immune responses were monitored 3 days after treatment in all mice by a flow cytometry-based assessment of inflammatory cell populations in blood samples and key organs (heart, spleen and bone marrow). Sixteen additional animals were sham-operated and also injected with EV, hiPSC-Pg or PBS (n=5-6 per group).ResultsIn vitro studieshiPSC-Pg-derived EV expectedly expressed stem cell markers (SSEA-1, c-Kit, CD184, CD133) and also low levels of HLA class I and CD274 (PD-L1). Mixed lymphocytereactions demonstrated that EV do not activate an adaptive allogeneic immune response since they failed to induce the proliferation of allogeneic CD8 or CD4 T cells. In contrast to their parental cells, EV did not induce NK cell degranulation, even at very high concentrations. In vivo studiesThe injection of hiPSC-Pg or their EV at the chronic post-infarction stage did not affect the number of T cells, B cells, and macrophages in the heart, spleen, bone marrow and blood, supporting an immune neutrality. However, at the acute stage, and in contrast to PBS, EV significantly reduced the number of macrophages M1 (p=0.0130), monocytes High (M1 precursors; p=0.0194) and neutrophils (p=0.0261) in cardiac tissue.ConclusionshiPS-Pg-EV look immunologically neutral in vitro and in vivo and seem even able to mitigate the inflammatory response seen at the acute stage of myocardial infarction. This suggests that immune suppression might not be necessary clinically, thereby adding to the attractiveness of hiPSC-Pg-EV as an acellular therapy for cardiac repair.