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

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 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.

Epicardial therapy with atrial appendage micrografts salvages myocardium after infarction

“…We Cell-based therapies and tissue engineering have long been investigated for their ability to deliver tissue regenerative adjuvant support. Atrial appendages were identified as niches for cardiac stem and progenitor cells and serve as a good autologous source of myocardial tissue for therapy due to their easy accessibility and relative redundancy for cardiac function (18,19).…”

“…However, in the AAM and ECM patch groups, the fall in LVEF seemed considerably smaller in magnitude than that observed in the MI group. The acute declines in LVEF at one-week time-point postoperatively in AAM patch, ECM patch and MI groups were as follows: 18.03 (from 54.49±2.93% to 36.69±2.56%), 19.77 (from 52.15±3.10% to 32.38±2.96%) and 34.94 percent points (from 58.72±2.58% to 23.78±3.16%), respectively, with significant difference perceptible only between AAM patch and MI groups. However, since prevention of acute HF seemed evident in both patch groups, we hypothesize a considerable protective effect to occur by direct mechanical support, i.e.…”

“…Nevertheless, cardiac progenitor cells have become a potential candidate for cell therapy (11,12), and these cells may be superior to other cell types in terms of regenerative effects (13,14). Although cardiac progenitor cells can be found in various locations throughout heart (12,(15)(16)(17), atrial tissues may contain the densest population (12,18,19). Moreover, cells isolated from atrial appendage tissues have demonstrated therapeutic potential (20).…”

Isolation and Characterization of Cardiac Mesenchymal Stromal Cells from Endomyocardial Bioptic Samples of Arrhythmogenic Cardiomyopathy Patients

“…To date, preclinical studies of regenerative medicine identified useful therapeutic potential in the C-MSC and their paracrine activity 18 22 23 . Importantly, clinical trials in which the cell source is the heart are underway either with cardiosfere-derived cells or with subpopulations of C-MSC 13 24 25 .…”

ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure

“…21,22,[24][25][26][27][28][29][30][31][32][33] Several specific interventions have been identified to improve the maturation of hPSCderived cardiomyocytes including (i) addition of thyroid hormone, 34 (ii) application of electrical stimulation, 33,35,36 , (iii) mechanical loading 21,27,[37][38][39] , or (iv) co-culture with cardiac-specific cell types including endothelial cells 22 and cardiac fibroblasts 21,31,[40][41][42] or a mixture of fibroblast-like stromal cells. 37,43 A good understanding of the optimal cellular make up as well as reliable quality markers for cardiomyocytes and non-myocyte maturation should be instrumental to further improve the sophisticated architecture and function engineered myocardium.…”