Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure


Autoři: Patricia van den Hoogen aff001;  Saskia C. A. de Jager aff001;  Emma A. Mol aff001;  Arjan S. Schoneveld aff003;  Manon M. H. Huibers aff004;  Aryan Vink aff004;  Pieter A. Doevendans aff006;  Jon D. Laman aff009;  Joost P. G. Sluijter aff001
Působiště autorů: Laboratory of Experimental Cardiology, UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands aff001;  Laboratory of Cardiovascular Cell Biology, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands aff002;  Laboratory of Clinical Chemistry & Haematology, ARCADIA, University Medical Center Utrecht, Utrecht, the Netherlands aff003;  Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands aff004;  Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands aff005;  Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands aff006;  Netherlands Heart Institute, Utrecht, the Netherlands aff007;  Central Military Hospital, Utrecht, the Netherlands aff008;  Department of Biomedical Sciences of Cells and Systems (BSCS), University Medical Center Groningen, Groningen, the Netherlands aff009
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227283

Souhrn

Upon myocardial damage, the release of cardiac proteins induces a strong antibody-mediated immune response, which can lead to adverse cardiac remodeling and eventually heart failure (HF). Stem cell therapy using mesenchymal stromal cells (MSCs) or cardiomyocyte progenitor cells (CPCs) previously showed beneficial effects on cardiac function despite low engraftment in the heart. Paracrine mediators are likely of great importance, where, for example, MSC-derived extracellular vesicles (EVs) also show immunosuppressive properties in vitro. However, the limited capacity of MSCs to differentiate into cardiac cells and the sufficient scaling of MSC-derived EVs remain a challenge to clinical translation. Therefore, we investigated the immunosuppressive actions of endogenous CPCs and CPC-derived EVs on antibody production in vitro, using both healthy controls and end-stage HF patients. Both MSCs and CPCs strongly inhibit lymphocyte proliferation and antibody production in vitro. Furthermore, CPC-derived EVs significantly lowered the levels of IgG1, IgG4, and IgM, especially when administered for longer duration. In line with previous findings, plasma cells of end-stage HF patients showed high production of IgG3, which can be inhibited by MSCs in vitro. MSCs and CPCs inhibit in vitro antibody production of both healthy and end-stage HF-derived immune cells. CPC-derived paracrine factors, such as EVs, show similar effects, but do not provide the complete immunosuppressive capacity of CPCs. The strongest immunosuppressive effects were observed using MSCs, suggesting that MSCs might be the best candidates for therapeutic targeting of B-cell responses in HF.

Klíčová slova:

Antibodies – Heart failure – Immune response – Immunosuppressives – Lymphocyte proliferation – Mesenchymal stem cells – Stem cells – Antibody production


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