Endomyocardial biopsy derived adherent proliferating cells—A potential cell source for cardiac tissue engineering

Haag, Marion; Linthout, Sophie Van; Schröder, Sebastian E.A.; Freymann, Undine; Ringe, Jochen; Tschöpe, Carsten; Sittinger, Michael

doi:10.1002/jcb.22433

Cited by 22 publications

(36 citation statements)

References 48 publications

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“…As reported previously, CardAP cells do not differentiate into cardiomyocytes in standard assays [Haag et al, 2010]. Here, for the first time, we analyzed whether these CardAP cells can induce cardiomyogenesis of other cell types.…”

Section: Human Cardap Cells Induced Cardiomyogenesis In Cell Linesmentioning

confidence: 82%

“…CardAP cells, as used in this study, are a fibroblast-like cell type, isolated from biopsies from the right-ventricle side of the interventricular septum of patients, in order to evaluate unexplained left-ventricular dysfunction [Haag et al, 2010]. Although this general diagnosis includes a lot of unknown parameters such as inflammation and oxidative stress stimuli, human CardAP cells have already reproducibly demonstrated a reduction of murine acute Coxsackievirus B3-induced myocarditis and increased heart function after intravenous injection [Miteva et al, 2011].…”

Section: Discussionmentioning

confidence: 99%

“…Biopsies were taken from the right-ventricle side of the interventricular septum and cells were isolated and culture expanded as described previously [Haag et al, 2010]. Briefly, biopsies were washed with PBS (Biochrom) and outgrowth culture was performed in Iscove's medium (Biochrom) supplemented with 10% human allogeneic serum (German Red Cross, Berlin) and 1% penicillin/streptomycin solution.…”

Section: Isolation and Cultivation Of Cardap Cellsmentioning

confidence: 99%

“…Human CardAP cells reduce murine acute Coxsackievirus B3-induced myocarditis and increase heart function after intravenous injection [Miteva et al, 2011]. However, they act in a paracrine fashion and do not differentiate into cardiomyocytes in standard assays [Haag et al, 2010;Miteva et al, 2011]. Here, the P19 and P19CL6 cell lines were applied to test their potential to induce cardiomyogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Secondly, we used the inducible properties of both cell lines to test the potential of human cardiac-derived adherent proliferating (CardAP) cells to induce cardiomyogenesis. CardAP cells are fibroblast-like cells that can be isolated from biopsies of the right-ventricle side of the interventricular septum [Haag et al, 2010]. Human CardAP cells reduce murine acute Coxsackievirus B3-induced myocarditis and increase heart function after intravenous injection [Miteva et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

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A P19 and P19CL6 Cell-Based Complementary Approach to Determine Paracrine Effects in Cardiac Tissue Engineering

Dehne

Adam²,

Materne³

et al. 2014

Cells Tissues Organs

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The negligible self-repair potential of the myocardium has led to cell-based tissue engineering approaches to restore heart function. There is more and more consensus that, in addition to cell development, paracrine effects in particular play a pivotal role in the repair of heart tissue. Here, we present two complementary murine P19 and P19CL6 embryonic carcinoma cell-based in vitro test approaches to study the potential of repair cells and the factors secreted by these cells to induce cardiomyogenesis. P19 cells were 3-dimensionally cultured in hanging drops and P19CL6 cells in a monolayer. Both systems, capable of inducible differentiation towards the cardiomyogenic lineage shown by the appearance of beating cells, the expression of connexin 43 and cardiac troponins T and I, were used to test the cardiomyogenesis-inducing potential of human cardiac-derived adherent proliferating (CardAP) cells, which are candidates for heart repair. CardAP cells in coculture as well as CardAP cell-conditioned medium initiated beating in P19 cells, depending on the cell composition and concentration of the medium. CardAP cell-dependent beating was not observed in P19CL6 cultures, but connexin 43 and cardiac troponin formation as well as expression of GATA-binding protein 4 indicated the dose-dependent stimulatory cardiomyogenic effect of human CardAP cells. In summary, in different ways, P19 and P19CL6 cells have shown their capability to detect paracrine effects of human CardAP cells. In a complementary approach, they could be beneficial for determining the stimulatory cardiomyogenic potential of candidate cardiac-repair cells in vitro.

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Section: Human Cardap Cells Induced Cardiomyogenesis In Cell Linesmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Isolation and Cultivation Of Cardap Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A P19 and P19CL6 Cell-Based Complementary Approach to Determine Paracrine Effects in Cardiac Tissue Engineering

Dehne

Adam²,

Materne³

et al. 2014

Cells Tissues Organs

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The atrial appendage as a suitable source to generate cardiac‐derived adherent proliferating cells for regenerative cell‐based therapies

Detert

Stamm

Beez

et al. 2017

J Tissue Eng Regen Med

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Cardiac-derived adherent proliferating (CardAP) cells obtained from endomyocardial biopsies (EMBs) with known anti-fibrotic and pro-angiogenic properties are good candidates for the autologous therapy of end-stage cardiac diseases such as dilated cardiomyopathy. However, due to the limited number of CardAP cells that can be obtained from EMBs, our aim is to isolate cells with similar properties from other regions of the heart with comparable tissue architecture. Here, we introduce the atrial appendage as a candidate region. Atrial appendage-derived cells were sorted with CD90 microbeads to obtain a CD90 cell population, which were subsequently analysed for their surface marker and gene expression profiles via flow cytometry and micro array analysis. Enzyme-linked immunosorbent assays for vascular endothelial growth factor and interleukin-8 as well as tube formation assays were performed to investigate pro-angiogenic properties. Furthermore, growth kinetic assays were performed to estimate the cell numbers needed for cell-based products. Microarray analysis revealed the expression of numerous pro-angiogenic genes and strong similarities to CardAP cells with which they also share expression levels of defined surface antigens, that is, CD29 , CD44 , CD45 , CD73 , CD90 , CD105 , and CD166 . High secretion levels of vascular endothelial growth factor and interleukin-8 as well as improved properties of vascular structures in vitro could be detected. Based on growth parameters, cell dosages for the treatment of more than 250 patients are possible using one appendage. These results lead to the conclusion that isolating cells with regenerative characteristics from atrial appendages is feasible and permits further investigations towards allogenic cell-based therapies.

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Immune attributes of cardiac-derived adherent proliferating (CAP) cells in cardiac therapy

Haag

Stolk

Ringe

et al. 2012

J Tissue Eng Regen Med

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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.

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Endomyocardial biopsy derived adherent proliferating cells—A potential cell source for cardiac tissue engineering

Cited by 22 publications

References 48 publications

A P19 and P19CL6 Cell-Based Complementary Approach to Determine Paracrine Effects in Cardiac Tissue Engineering

A P19 and P19CL6 Cell-Based Complementary Approach to Determine Paracrine Effects in Cardiac Tissue Engineering

The atrial appendage as a suitable source to generate cardiac‐derived adherent proliferating cells for regenerative cell‐based therapies

Immune attributes of cardiac-derived adherent proliferating (CAP) cells in cardiac therapy

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