Marrow Contributes to Kidney Vasculogenesis in Humans.

Abstract

The hematopoietic stem cell (HSC) is capable of contributing to vasculogenesis in response to ischemic injury. We have previously demonstrated that adult hemangioblast activity also exists within the capabilities of human hematopoietic stem/progenitor cells (HSC/HPC). However, we question the clinical relevance of adult hemangioblast activity. Thus, to address this question, we sought to analyze the marrow contribution to blood vessels within damaged vascular beds. Given the nephrotoxic side effects of chemotherapy and hematopoietic cell transplantation regimens, we identified kidney tissues from women (n=4) who received hematopoietic cell transplantations from male donors. Kidney tissues were stained for CD31, CD45, and XY FISH. One hundred forty vascular fields were analyzed. Fields were divided into three zones based on physiologic functions: glomerular, arteriolar (afferent & efferent), and medullary. In ever zone we identified male/marrow-derived endothelial cells contributing to kidney vasculature. However, each zone differed as to the degree of male/marrow-derived vascular contribution. In the glomerular regions, 36% of glomeruli contained one or more marrow-derived endothelial cells, as determined by orientation at the lumen edge, CD31 surface expression, and Y chromosome staining. In contrast, only 4% of arterioles contained male/marrow-derived endothelial cells. In the medulla, 9% of blood vessels contained male/marrow-derived blood vessels. The median number of marrow-derived endothelial cells in all regions was 1 male cell per blood vessel in field. In conclusion, human marrow can contribute modestly to kidney vasculature, especially in glomeruli. These results expose a potential strategy of kidney vessel repair by illuminating marrow-derived vasculogenesis within the kidney.