Transplanted human bone marrow contributes to vascular endothelium

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Abstract
Recent evidence indicates that bone marrow is a source of endothelial progenitor cells that are mobilized into the peripheral blood in response to cytokines or tissue injury. Previously, we showed that functional endothelial cells (ECs) can be clonally derived from phenotypically defined hematopoietic stem cells. To determine the EC potential of human bone marrow and peripheral blood stem cells, blood vessels in sex-mismatched transplant recipients were evaluated. EC outcomes were identified by using a combination of immunohistochemistry and XY interphase FISH. Donor-derived ECs were detected in the skin and gut of transplant recipients with a mean frequency of 2% and could readily be distinguished from CD45-expressing hematopoietic stem cells. None of the >4,000 ECs examined had more than two sex chromosomes, consistent with an absence of cell fusion. Y chromosome signals were not detected in sex-matched female recipients, excluding the vertical transmission of male cells. None of the recipients evaluated before hematopoietic engraftment demonstrated donor-derived ECs, indicating a close linkage between the recovery of hematopoiesis and EC outcomes. Transplantable bone marrow-derived endothelial progenitor cells may represent novel therapeutic targets for hematopoietic and vascular disease.