Identification Of Novel Circulating Multipotent Stem Cells In Human Peripheral Blood, Which Originate From Human Heart

Background: There has been only one study showing the presence of multipotent stem cells in bone marrow, called multipotent adult progenitor cells (MAPCs). These cells can be differentiated not only into mesenchymal lineage cells, but also into cells with neuroectoderm or endoderm features. Until recently, however, there has been no report isolating and characterizing these cells from human peripheral blood. Here, we hypothesized that there might be circulating multipotent stem cells in human peripheral blood. In addition, we tried to find the origin of these cells. Methods and Results: From human peripheral blood mononuclear cells adherent on non-coated dishes, we could identify new population of cells, which are quite distinct from previously reported other stem cells. Newly identified cells have the gene profiles such as Oct3/4, KLF4, and c-Myc, suggesting multipotent stemness. Moreover, FACS analysis demonstrated that these stem cells have the property of mesenchymal stem cells. With diverse differentiation media, we could differentiate these cells into endothelial-like cells or vascular smooth muscle-like cells. These stem cells have the properties of osteogenic, adipogenic, and myogenic differentiation. Moreover, these cells can be differentiated into ectodermal lineage cells such as neuron-like cells as well as endodermal lineage cells such as hepatocyte-like cells. When injected into the mouse heart in vivo , these newly identified stem cells could be differentiated into endothelial cells, smooth muscle cells, and cardiomyocytes. To investigate the origin of these cells, we collected peripheral mononuclear cells from patients receiving the transplantation of bone marrow, liver, heart, or kidney. After culturing these cells and identifying HLA type of each cells, we could confirm that these stem cells are derived from human heart. Conclusion: This study showed the presence of novel circulating multipotent stem cells in human peripheral blood. Interestingly, these cells are derived from human heart. These findings suggest that these cells can be easily obtained from human peripheral blood and used for regenerative medicine in real world.