Identification of tissue-specific vasculogenic cells originating from murine uterus

Endometrium is a highly regenerative adult tissue that undergoes repeated degeneration and regeneration following menarche. Therefore, it is believed that endometrium contains stem and/or progenitor cells in order to compensate for the regeneration of tissue components. We report here that stem-like cells having vasculogenic potential are present in the uterus. Enzymatically extracted cells from murine uteri were characterized and fractionated into four subpopulations by flowcytometry; CD34⁺/45^- (Ut-34), CD34^-/45^- (UtDN) and the remaining CD45⁺ cell fractions (CD34⁺/ 45⁺ and CD34^-/45⁺ cells). The Ut-34 and Ut-DN fractions were mostly negative for putative endothelial cell (EC) markers, such as CD31, Flk-1, c-kit and VE-cadherin, although the Ut-DN fraction contained 2.8% CD31⁺ cells. Ut-DN cells were further divided into CD31⁺ and CD31^- fractions. Three cell populations were obtained from green fluorescence protein (GFP) transgenic mice and were transplanted into injured wildtype mouse skeletal muscle. At 4 weeks after cell transplantation, donor-derived vascular smooth muscle and ECs were observed in the injured recipient muscle. A similar trend was observed in the Ut-34 group, but differentiation into vascular smooth muscle was predominant. In contrast, the Ut-DN/31⁺ cell-transplanted group showed preferential differentiation into vascular ECs, thus suggesting that they were relatively committed preexisting ECs. These characteristics were also seen in vitro, in clonal cell cultures. Interestingly, donor derived Ut-DN/31 ⁺, Ut-DN/31^- and Ut-34 cells could not be identified after bone marrow (BM) transplantation, thus confirming that they are not derived from BM. It therefore appeared that tissue-specific vasculogenic cells are present in the murine uterus and that they exhibit vascular formation, even in different tissue microenvironments.