Endogenous origin of glomerular endothelial and mesangial cells in grafts of embryonic kidneys

Abstract

To address origins of glomerular endothelial and mesangial cells in embryonic mammalian kidneys, we established interspecies grafts between rats and mice, in which fetal kidneys were implanted into the anterior eye chamber of adult hosts. After 5-7 days, hosts bearing grafts received intravenous injections with species-specific monoclonal antibodies (MAbs) to matrix components. In all cases, glomerular basement membranes and mesangial matrices labeled solely for donor-derived matrix. Additionally, microvessel extracellular matrices within grafts were usually of donor origin. To examine directly the origin of glomerular endothelial and mesangial cells, we grafted embryonic gestational days 11-12 (E11-12) kidneys from normal mice into anterior eye chambers of host reverse-orientation splice acceptor 26 mice, which are transgenic animals that express beta-galactosidase in every cell. When grafts were developed for beta-galactosidase activity, host cells were seen in peripheral vessels, but the majority of glomerular endothelial cells were of donor, not host, origin. Where host-derived-endothelial cells were found in glomeruli, donor endothelial cells were present as well. Mesangial cells were always of donor origin. When E11 mouse kidneys were labeled with the endothelial cell-specific Bandeiraea simplicifolia isolectin B4, we determined that endothelial cells are present from the inception of metanephrogenesis. Together, the evidence shows that cells of endogenous kidney origin were almost entirely responsible for development of the glomerular microvasculature in oculo. External vessels from the host, although important for graft maintenance, were not major contributors to the glomerulus.

Functional Genetic Targeting of Embryonic Kidney Progenitor Cells Ex Vivo

“…As expected, the GFP + MM cells within the cultured chimeric explants had the capacity to incorporate to the epithelial tubules ( Figure 4 40,41 and FACS. In the organ culture condition, the Foxd1 + cells also remain distinct from the Pax2 + ones representing the nephron precursors ( Figure 5, A-D).…”

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

“…[23][24][25] Whereas our studies suggest that SCL+ precursors originate locally in the kidney, the fact that we found cells derived from the SCL+ precursors labeled at E6.5 or E9.5, before the kidney starts to form, indicates the possibility that precursors from the yolk sac and AGM may have seeded the intermediate mesoderm before the condensation and development of the "avascular" metanephric mesenchyme.…”

Development of the Renal Arterioles

“…Interspecies cross transplantation experiments of prevascular embryonic kidneys were originally performed into quail chorioallantoic membrane because of the presence of a characteristic quail nuclear marker that could easily track the contribution of the host tissue. 25,35 Those experiments show the presence of hostderived ECs and mesangial cells within the embryonic kidney and suggest an extrarenal source for ECs and mesangial cells. The development of genetically-labeled mice with traceable reporters allowed further experiments in mice.…”

“…It is also clear that those precursors differentiate into all of the cell types necessary for the development of the kidney arterioles, including endothelial cells (ECs), smooth muscle cells (SMCs), and renin cells. 24,25 Furthermore, crosstransplantation studies of those embryonic prevascular kidneys under the kidney capsule of a host mouse allowed us and others to demonstrate that precursor cells have the capacity to differentiate, acquire the right positional information, and fully assemble to form the kidney arterioles. 24 The origin, lineage relationships, and morphogenesis of the kidney vasculature are also not well understood.…”