CD34 and CD49f Double-Positive and Lineage Marker-Negative Cells Isolated from Human Myometrium Exhibit Stem Cell-Like Properties Involved in Pregnancy-Induced Uterine Remodeling

ABSTRACT Repeated and dramatic pregnancy-induced uterine enlargement and remodeling throughout reproductive life suggests the existence of uterine smooth muscle stem/ progenitor cells. The aim of this study was to isolate and characterize stem/ progenitor-like cells from human myometriumthrough identification of specific surface markers. We here identify CD49f and CD34as markers to permit selection of the stem/ progenitor cell-like population from human myometriumand show that human CD45– CD31– glycophorinA– and CD49f+ CD34+ myometrial cells exhibit stem cell-like properties. These include side populationphenotypes, an undifferentiated status, high colony-forming ability, multilineage differentiation into smooth muscle cells, osteoblasts, adipocytes, and chondrocytes, and in vivo myometrial tissue reconstitution following xenotransplantation. Furthermore, CD45– CD31– glycophorinA– and CD49f+ CD34+ myometrial cells proliferate under hypoxic conditions in vitro and, compared with the untreated nonpregnan...