Using morphometric analysis, endothelium volume density of Ruxolitinib molecular weight peritubular capillaries of 31 week-old MWF rats significantly increased compared to areas SCH772984 distant from the metanephroi. The length density of peritubular capillaries in areas adjacent to the graft significantly increased compared to distant ones in animals grafted with metanephroi. A representative image, at low magnification, showing the area affected by vascular changes in grafted male animals is supplied in S1 Fig. In femaleMWF, the development of metanephroi did not affect either peritubular capillary Vv or Jv of recipient kidneys in areas adjacent to or distant from the graft. The expression of several genes and related proteins relevant to kidney regeneration was studied in host renal tissues of animals receiving metanephroi in the adjacent areas compared to saline. A remarkable increase in mRNA expression of growth factors including VEGF, FGF2, HGF, IGF-1 was observed in renal tissues rats with metanephros transplants compared to saline. Moreover, transcription factor Pax-2 was significantly upregulated. Consistent with mRNA expression data, immunohistochemical analysis confirmed that protein expression of the growth factors clearly increased in renal tissues adjacent to MET compared to saline, the same area that was associated with improved vascularization. Moreover, Pax-2 was expressed in several tubuli of metanephros- graft animals whereas they were rare or absent in saline-treated rats. In contrast, in female MWF rats we did not observe significant metanephros-induced changes in protein expression of any of the growth or transcription factors studied. Both in male and female animals, we have not observed immunohistochemical differences in the expression of growth/transcription factors between renal tissues of animals receiving saline or MET in areas distant from the graft. New technologies based on tissue engineering approaches are enlivening the challenge to find a solution for the treatment of severely injured organs. The approaches of developing new kidneys starting with either renal primordia transplanted under the kidney capsule or organoids obtained from an embryonic renal cell suspension are promising methodologies. However, it was not clear to which extent the environment of chronically injured tissue of the host could influence graft development. In end-stage renal failure, reduced vascularization deriving from chronic hypoxia is associated with severe oxidative damage and fibrosis which may hamper anlagen sprouting. Our present study goes a step further towards what has been reported in healthy animals and proves that metanephroi transplanted under the kidney capsule of rats with progressive kidney disease undergo successful organogenesis with development into functional nephrons. In MWF rats, a model of progressive nephropathy, developed grafts are functionally active and can primitively produce urine as suggested by the higher concentration of creatinine in the cyst-like structure formed in the graft compared to levels in the blood. Well-formed glomerular capillary tufts and small vessels of the graft are connected with host circulation as proved by the presence of systemically injected fluorescein-labeled BSA in vessels and capillary tufts of neo-kidneys. Moreover, fluorescent BSA is found in tubular structures of the graft, showing the capacity of tubuli to absorb labeled protein. Altogether these data indicate that chronically injured kidneys allow the development of grafted metanephroi and have the potential to establish functional interactions with the graft.