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Updated: May 24, 2026
Isolation of Perivascular Multipotent Precursor Cell Populations from Human Cardiac Tissue
Published on: October 8, 2016
Immune attributes of cardiac-derived adherent proliferating (CAP) cells in cardiac therapy
Marion Haag1, Meaghan Stolk, Jochen Ringe
1Berlin-Brandenburg Centre for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany; Tissue Engineering Laboratory, Charité-Universitätsmedizin Berlin, Germany.
Insights
Cardiac-derived adherent proliferating (CAP) cells show low immunogenicity for potential heart disease therapy. These cells reduce inflammatory cytokines and promote regulatory T cells, suggesting a promising role in cardiac repair.
Area of Science:
- Cardiovascular Research
- Immunology
- Regenerative Medicine
Background:
- Cardiac cell therapies aim to improve heart disease outcomes.
- Low immunogenicity is crucial for allogeneic cell sources.
- Cardiac-derived adherent proliferating (CAP) cells require immunogenicity assessment.
Purpose of the Study:
- To evaluate the immunogenicity and immune modulatory properties of CAP cells in vitro.
- To determine if CAP cells induce immune cell proliferation or activation.
- To assess CAP cells' potential to generate regulatory T cells (Tregs).
Main Methods:
- Human CAP cells isolated from cardiac biopsies.
- Co-culture assays with PHA-stimulated PBMCs and MLCs.
- Flow cytometry for proliferation, activation, and FoxP3+ Treg analysis.
- Cytokine level analysis (TNFα, IFNγ) in supernatants.
Main Results:
- CAP cells demonstrated low immunogenicity with allogeneic PBMCs.
- CAP cells did not alter normal alloantigen-driven immune responses in MLCs.
- CAP cells significantly reduced PHA-induced immune cell proliferation.
- CAP cells decreased TNFα and IFNγ levels.
- CAP cells promoted the generation of Tregs.
Conclusions:
- CAP cells exhibit low immunogenicity.
- CAP cells possess immune modulatory features, reducing inflammation.
- CAP cells induce regulatory T cells.
- CAP cells hold promise for cardiac repair strategies.
Abstract:
Cardiac-directed cell therapies show potential to reduce mortality and morbidity in heart disease. However, high functional efficacy should be complimented with low immunogenicity, in particular if allogeneic cell sources are applied. Therefore, we aimed to examine cardiac-derived adherent proliferating (CAP) cells with respect to their immunogenicity and immune modulatory features in vitro. Human CAP cells were isolated from cardiac biopsies and screened in a CFSE-based proliferation assay in co-cultures with phytohaemagglutinin (PHA)-stimulated human peripheral blood lymphocytes (PBMCs) or mixed lymphocyte cultures (MLCs) to assess their potential to induce immune cell proliferation or activation by flow cytometry. Moreover, levels of pro- and anti-inflammatory cytokines in supernatants of co-cultures were analysed. The capacity of CAP cells to induce the generation of regulatory T cells (Tregs) was determined by flow cytometric measurement of FoxP3 expression. CAP cells of different donors (n = 5) showed low immunogenicity in co-cultures with human allogeneic PBMCs. In addition, they induced no change in the normal alloantigen-driven immune responsiveness in MLCs. However, CAP cells significantly reduced the induction of immune cell proliferation in PBMCs cultures stimulated with the polyclonal trigger PHA. Adding CAP cells into MLCs or PHA-stimulated cultures resulted in significantly reduced levels of TNFα or IFNγ, respectively, compared to controls without CAP cells. At early time points (day 2), interaction of CAP cells with PBMCs resulted in elevated proportions of FoxP3+ CD4+ CD25(high+) cells. The results indicate that CAP cells have low immunogenicity and could be advantageous in cardiac repair by reducing inflammatory cytokines and inducing regulatory T cells.
