Novel population of human monocyte and osteoclast progenitors from pluripotent stem cells and peripheral blood

Abstract

Abstract Osteoclasts are multinuclear cells of monocytic lineage, with the ability to resorb bone. Studies in mouse have identified bone marrow clonal progenitors able to generate mature osteoclast cells (OCs) in vitro and in vivo. These osteoclast progenitors (OCPs) can also generate macrophages and dendritic cells. Interestingly, cells with equivalent potential can be detected in periphery. In humans, cells with OCP activity have been identified in bone marrow and periphery; however, their characterization has not been as extensive. We have developed reproducible methods to derive, from human pluripotent stem cells, a population containing monocyte progenitors able to generate functional OCs. Within this population, we have identified cells with monocyte and osteoclast progenitor activity based on CD11b and CD14 expression. A population double positive for CD11b and CD14 contains cells with expected osteoclastic potential. However, the double negative (DN) population, containing most of the hematopoietic progenitor activity, also presents a very high osteoclastic potential. These progenitor cells can also be differentiated to macrophage and dendritic cells. Further dissection within the DN population identified cells bearing the phenotype CD15−CD115+ as the population with highest monocytic progenitor and osteoclastic potential. When similar methodology was used to identify OCPs from human peripheral blood, we confirmed a published OCP population with the phenotype CD11b+CD14+. In addition, we identified a second population (CD14−CD11bloCD115+) with high monocytic progenitor activity that was also able to form osteoclast like cells, similar to the 2 populations identified from pluripotent stem cells.