Extracellular matrix and capillary ingrowth in interspecies chimeric kidneys

Abstract

The migration of capillaries into mouse embryonic kidneys grafted on quail chorioallantoic membrane (CAM) was analyzed by two monoclonal antibodies against quail endothelial and haematopoietic cells. As shown by immunohistochemistry, the quail chorioallantoic vessels invaded the kidney explant. Initially, the capillaries were detected in the interstitial stroma and, soon thereafter, tightly adjacent to the branches of the ureteric bud. The induced mesenchymal cell condensates, the prospective nephric vesicles, were avascular, but when the early S-shaped body was formed, the capillaries invaded its lower crevice. Finally chimeric glomeruli consisting of mouse podocytes and quail endothelial cells, were formed and, contemporarily, the capillaries ceased to migrate. Within the endothelial-mesangial area of the chimeric glomeruli, all cells expressed the quail-type nuclear structure and were stained by the quail endothelial-specific antibodies. The pattern of migrating capillaries was compared to the distribution of the extracellular matrix (ECM) molecules by double staining with polyclonal antibodies against laminin or fibronectin, and monoclonal quail endothelial-specific antibodies. Initially, the capillaries migrated in a fibronectin-rich matrix, devoid of laminin, but when the epithelial kidney tubules formed, some capillaries attached to the newly formed epithelial basement membrane. At no stage were the capillaries seen to penetrate the epithelial basement membrane. The orderly branching of the ureteric bud, followed by the formation of nephrons and the shift in the ECM, might create pathways for an oriented capillary migration. The fibronectin-rich areas could be a scaffold for the capillary migration, and the attachment to the basement membranes a means for their cessation.