Abstract 17167: Identification of Circulating Stem Cells Originating From the Endocardium of the Human Heart
Background: There have been several studies showing the presence of cardiac stem cells in myocardium and epicardial progenitor cells in epicardium, respectively. Until recently, however, there has been no report showing the presence of stem cells in the endocardium. In this study, we identified circulating multipotent stem cells from human peripheral blood. Furthermore, we investigated the origin of these cells and the differentiation potential in vivo.
Methods and Results: From human peripheral blood mononuclear cells grown on non-coated dishes, we identified a new population of cells, which were quite distinct from previously reported other stem cells. Newly identified cells had the gene profiles such as Oct3/4, KLF4, Nanog, and c-Myc. Moreover, FACS analysis excluded the possibility that these cells might be hematopoietic stem cells. To investigate the origin of these cells, we collected peripheral blood from patients receiving the transplantation of bone marrow, liver, heart, or kidney. After culturing these cells, we could confirm that these stem cells were derived from the human heart by identifying the HLA types or the STR (short tandem repeat) profiles. In addition, we demonstrated that Nuclear Factor of Activated T-cells (NFAT)-positive and CD31-positive circulating cells in peripheral blood were derived from NFAT-positive cells in the endocardium. These cells had multipotency, indicating the ability of differentiation not only into mesodermal lineages, but also into ectodermal or endodermal lineages. When injected into the mouse heart in vivo, these stem cells were differentiated into multiple lineages, resulting in the improvement of the function. We established more than 100 cell lines from peripheral blood of patients with coronary artery diseases, cardiomyopathies, hematologic diseases, liver diseases, and kidney diseases.
Conclusions: Our study showed the existence of novel circulating multipotent stem cells in human peripheral blood, which express NFAT. Interestingly, these cells are derived from the tissue-resident stem cells of the heart endocardium. Our findings suggest that these stem cells obtainable from peripheral blood could be a promising tool for regenerating damaged heart.
- © 2013 by American Heart Association, Inc.