Dataset Information

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes.

ABSTRACT:

Background

Nano-sized vesicles, so called extracellular vesicles (EVs), from regenerative cardiac cells represent a promising new therapeutic approach to treat cardiovascular diseases. However, it is not yet sufficiently understood how cardiac-derived EVs facilitate their protective effects. Therefore, we investigated the immune modulating capabilities of EVs from human cardiac-derived adherent proliferating (CardAP) cells, which are a unique cell type with proven cardioprotective features.

Results

Differential centrifugation was used to isolate EVs from conditioned medium of unstimulated or cytokine-stimulated (IFN?, TNF?, IL-1?) CardAP cells. The derived EVs exhibited typical EV-enriched proteins, such as tetraspanins, and diameters mostly of exosomes (+ cells as major recipient cell subset of CardAP-EVs. This interaction caused a significant lower surface expression of HLA-DR, CD86, and increased expression levels of CD206 and PD-L1. Additionally, EV-primed CD14⁺ cells released significantly more IL-1RA. Notably, CardAP-EVs failed to modulate anti-CD3 triggered T cell proliferation and pro-inflammatory cytokine release in monocultures of purified CD3⁺ T cells. Subsequently, the immunosuppressive feature of CardAP-EVs was restored when anti-CD3 stimulated purified CD3⁺ T cells were co-cultured with EV-primed CD14⁺ cells. Beside attenuated T cell proliferation, those cultures also exhibited a significant increased proportion of regulatory T cells.

Conclusions

CardAP-EVs have useful characteristics that could contribute to enhanced regeneration in damaged cardiac tissue by limiting unwanted inflammatory processes. It was shown that the priming of CD14⁺ immune cells by CardAP-EVs towards a regulatory type is an essential step to attenuate significantly T cell proliferation and pro-inflammatory cytokine release in vitro.

SUBMITTER: Beez CM

PROVIDER: S-EPMC6537224 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes.

Beez Christien M CM Haag Marion M Klein Oliver O Van Linthout Sophie S Sittinger Michael M Seifert Martina M

Journal of nanobiotechnology 20190527 1

<h4>Background</h4>Nano-sized vesicles, so called extracellular vesicles (EVs), from regenerative cardiac cells represent a promising new therapeutic approach to treat cardiovascular diseases. However, it is not yet sufficiently understood how cardiac-derived EVs facilitate their protective effects. Therefore, we investigated the immune modulating capabilities of EVs from human cardiac-derived adherent proliferating (CardAP) cells, which are a unique cell type with proven cardioprotective featur ...[more]

PMID: 31133024

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Dataset Information

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes.

Background

Results

Conclusions

Publications

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes.

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