Endometrial Endothelial Cells are Derived From Donor Stem Cells in a Bone Marrow Transplant Recipient

The uterine endometrium is a highly dynamic, cyclically regenerating, richly vascularized tissue. The source of new endothelial cells (ECs) for vascular regrowth remains uncertain, and it is not clear whether endothelial progenitor cells (EPCs) derived from the bone marrow contribute to angiogenesis in the human endometrium. The rare occurrence of pregnancy and subsequent normal menstruation following bone marrow transplantation (BMT) provided an opportunity to explore the role of marrow-derived EPCs in endometrial angiogenesis. Endometrial biopsies were taken from a woman aged 30 with aplastic anemia following nonmyeloablative allogeneic BMT using a brother’s cells, and also from 2 control women having cesarean section. The index patient menstruated normally, became pregnant 2 years after BMT, and had a cesarean section at 36 weeks’ gestation. Biopsied tissue was examined immunohistochemically for CD34 and VEGFR2 antibodies for immunophenotyping of ECs, and FISH (fluorescence in situ hybridization) probes were used to detect donor cells. Chimerism was evaluated by the real-time polymerase chain reaction technique. A parallel study was carried out in female mice given a hematological stem cell transplant. At the time of cesarean section, an average of 14% of endometrial ECs were donor-derived. The figure 12 months later was 10%. Neither of the 2 nontransplanted female control women exhibited a mismatch in endometria at the time of cesarean section. In biopsies taken from female mice 40 days after stem cell transplantation, the average proportion of donor-derived ECs was 6%. The investigators conclude from these findings that, in the endometrium, bone marrow-derived EPCs contribute to the formation of new blood vessels. Endometrial biopsy is a feasible and cost-effective means of studying bone marrow-derived EPCs.