Abstract
Background. Human cardiac-derived progenitor cells (hCPCs) have shown promise in treating heart failure (HF) in adults. The purpose of this study was to describe derivation of hCPCs from pediatric patients with end-stage HF. Methods. At surgery, discarded right atrial tissues (hAA) were obtained from HF patients (n = 25; hAA-CHF). Minced tissues were suspended in complete (serum-containing) DMEM. Cells were selected for their tissue migration and expression of stem cell factor receptor (hc-kit). Characterization of hc-kitpositive cells included immunohistochemical screening with a panel of monoclonal antibodies. Results. Cells, including phase-bright cells identified as hc-kitpositive, spontaneously emigrated from hAA-CHF in suspended explant cultures (SEC) after Day 7. When cocultured with tissue, emigrated hc-kitpositive cells proliferated, first as loosely attached clones and later as multicellular clusters. At Day 21~5% of cells were hc-kitpositive. Between Days 14 and 28 hc-kitpositive cells exhibited mesodermal commitment (GATA-4positive and NKX2.5positive); then after Day 28 cardiac lineages (flk-1positive, smooth muscle actinpositive, troponin-Ipositive, and myosin light chainpositive). Conclusions. C-kitpositive hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kitpositive cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro.
Highlights
IntroductionThe human heart is thought to possess some regenerative potential
In the current era, the human heart is thought to possess some regenerative potential
In the pediatric age group, congenital heart disease (CHD) and cardiomyopathies are the predominate causes of heart failure leading to heart transplantation [8], with far fewer due to ischemic heart disease when compared with the adult age group [8]
Summary
The human heart is thought to possess some regenerative potential. Experimental evidence based on genetic fate mapping confirms that cardiac-derived stem or precursor cells (CPCs) contribute to replacement of adult mammalian cardiomyocytes [1]. These innate CPCs possess properties of stem cells, they are clonogenic, selfrenewing, capable of asymmetric division, express stem cell markers (i.e., stem cell antigen receptor or c-kit), and are capable of differentiating into cells of the cardiac lineages, including endothelial cells, smooth muscle cells, conduction cells, and cardiomyocytes [2]. Human cardiac-derived progenitor cells (hCPCs) have shown promise in treating heart failure (HF) in adults. C-kitpositive hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kitpositive cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro
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