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Published on: March 19, 2013
The atrial appendage as a suitable source to generate cardiac-derived adherent proliferating cells for regenerative
Stephan Detert1, Christof Stamm2, Christien Beez3
1Tissue Engineering Laboratory, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Insights
Researchers identified atrial appendage cells as a promising source for cardiac regenerative therapy. These cells exhibit anti-fibrotic and pro-angiogenic properties, offering a scalable alternative to limited endomyocardial biopsy-derived cells for treating heart disease.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Cell Therapy
Background:
- Cardiac-derived adherent proliferating (CardAP) cells from endomyocardial biopsies (EMBs) show therapeutic potential for end-stage cardiac diseases.
- Limited CardAP cell yield from EMBs restricts autologous therapy scalability.
- Alternative cardiac cell sources are needed for effective cell-based cardiac repair.
Purpose of the Study:
- To investigate the atrial appendage as a novel source for cardiac regenerative cells.
- To characterize atrial appendage-derived cells for anti-fibrotic and pro-angiogenic properties.
- To assess the potential of atrial appendage cells for autologous and allogeneic cell therapies.
Main Methods:
- Isolation and CD90 microbead sorting of atrial appendage cells.
- Flow cytometry and microarray analysis for surface marker and gene expression profiling.
- Enzyme-linked immunosorbent assays (ELISAs) for growth factor secretion and in vitro tube formation assays for angiogenic potential.
Main Results:
- Atrial appendage-derived cells (CD90low) share surface marker and gene expression profiles with CardAP cells.
- High secretion of vascular endothelial growth factor and interleukin-8 observed.
- Demonstrated pro-angiogenic properties in vitro, with potential for large-scale cell production.
Conclusions:
- Atrial appendages are a feasible source of cardiac cells with regenerative potential.
- These cells exhibit properties suitable for treating cardiac diseases like dilated cardiomyopathy.
- Findings support further investigation into allogeneic cell-based therapies using atrial appendage-derived cells.
Abstract:
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 CD90low 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+ , CD90low , 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.
