Transplanted Human Bone Marrow Contributes to Vascular Endothelium.

Accumulating evidence indicates that bone marrow is a source of endothelial progenitor cells. Recently our laboratory has shown that functional endothelial cells (EC) can be clonally derived from phenotypically defined hematopoietic stem cells. To determine the endothelial cell potential of human hematopoietic cells, blood vessels in skin and gut biopsies from sex-mismatched allogeneic transplant recipients were examined. H&E sections were initially reviewed to ensure tissue integrity and the absence of significant graft versus host disease. Coded biopsy specimens from 12 sex-mismatched transplant recipients and 6 sex-matched female transplant recipients were evaluated in a blinded fashion. Endothelial cells were identified using a combination of immunohistochemistry (IHC) and XY interphase FISH. Tissues sections were first evaluated by IHC for EC markers (CD31 or vWF) and for the pan-hematopoietic marker CD45 then assayed by dual-color interphase FISH for donor derived cells (XY). Tissue samples from each recipient were assayed at least 3 times by sequential IHC/FISH. The frequency of CD31⁺, CD45⁻, Y⁺ cells and vWF⁺, CD45⁻, Y⁺ cells in biopsies from the 18 transplant recipients was evaluated by 2 independent observers. 9 of 12 sex-mismatched recipients showed evidence of donor-derived Y chromosome positive EC. The remaining 3 recipients did not exhibit hematopoietic engraftment at the time of biopsy. Donor derived endothelial cells were detected in the skin and the gut of transplant recipients with a mean frequency of 2.3% (range 0.9–3.9). Donor derived hematopoietic cells including intraepithelial lymphocytes and tissue macrophages were excluded by CD45 expression. None of the >4,000 endothelial cells examined had >2 sex chromosomes, consistent with an absence or very low incidence of cell fusion. In addition, Y chromosome signals were not detected in sex matched female recipients, thereby excluding vertical transmission of male cells. Furthermore, none of the recipients evaluated prior to hematopoietic engraftment had detectable donor derived endothelial cells, indicating a close linkage between the recovery of hematopoiesis and endothelial cell outcomes. Our results suggest that the close association between hematopoiesis and the vascular system originally identified during early development persists into adult life. Consequently it will be important to study the potential therapeutic role of bone marrow derived endothelial cells in the setting of hematopoietic and vascular disease.