Decellularized kidney scaffold alters the healing response in chronic renal failure.

Decellularized (DC) kidney scaffold shows great potential for renal recovering. Our study explored the effect of the DC kidney scaffolds treating on chronic renal failure (CRF) through grafting them on 5/6 nephrectomized (5/6 Nx) rat kidneys compared with gelatin sponges covered the incision edges. Blood urea nitrogen and angiotensin II were significantly lower in most time in scaffold-grafted groups. Remnant kidney tumor necrosis factor-α and fibroblast growth factor in scaffold-grafted groups significantly reduced in majority of time points compared with controls. But platelet-derived growth factor-BB showed a different varied tendency, first higher in scaffold groups on week 2, 4, 6, but lower on week 8, finally no difference on week 12 compared with gelatin-sponge groups. In addition, the index of glomerular sclerosis was significantly lesser in scaffold-grafted groups, and, the accumulation of collagen III and collagen IV decreased in scaffold-grafted groups on week 6, 8, 12 compared with gelatin-sponge groups. Moreover, DC scaffolds enhanced the expression of CD133 on week 2, 6, 8, 12. In conclusion, DC kidney scaffold altered the healing response after 5/6 nephrectomy and ameliorated renal injury to some degree. Therefore, DC kidney scaffold could be a promising therapeutic method on CRF.

Analysis of structural components of decellularized scaffolds in renal fibrosis.

Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure. It is very promising to find the strategies to slow or even prevent the progression of fibrosis. This study focused on whether renal fibrosis decellularized scaffolds has the potential to be a model of cellular mechanisms of tissue fibrosis or donors for tissue engineering. In order to evaluate the feasibility of decellularized scaffolds derived from pathological kidneys, histology, proteomics and ELISA will be used to analysis the changes in the structure and main components of fibrotic tissue. The fibrosis model in this paper was induced by adenine-fed and the results showed that the structure of fibrotic scaffold was changed and some protein were up-regulated or down-regulated, but the cytokines associated with renal regeneration after injury were remained. In cell experiments, endothelial progenitor cells proliferated well, which proved that the fibrotic scaffolds have non-cytotoxic. All these conclusions indicate that the renal fibrosis decellularized scaffolds model has the ability to study fibrosis mechanism and the potential to be engineering donors as well as normal scaffolds.

EPCs enhance angiogenesis in renal regeneration.

Decellularized renal scaffolds have previously been used for renal regeneration following partial nephrectomy, in which angiogenesis played a key role. In this study, rats underwent partial nephrectomy and repaired with decellularized renal scaffolds. Subsequently, the labeled EPCs were intravenously injected into rats in EPCs group, and the control group received an equal amount of phosphate-buffer saline (PBS). We chose 1, 2 and 4 weeks post operation as time point. Average microvascular density (aMVD) analyses revealed higher angiogenesis in EPCs group compared with the control group. The expression of angiogenic growth factors including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and hypoxia-inducible factors 1-alpha (HIF-1α), was generally higher in the EPCs group in all weeks (1, 2 and 4), and peaked in week 2. EPCs were observed to home into renal injury site, promoting angiogenesis across the renal parenchyma-scaffold interface to be potentially used as bridges for EPCs to migrate into the implanted scaffolds. Administration of exogenous EPCs promotes angiogenesis and vasculogenesis in decellularized renal scaffolds-mediated renal regeneration, providing adequate microenvironment for kidney recovery post renal injury.

The angiogenesis in decellularized scaffold-mediated the renal regeneration.

There are increasing numbers of patients underwent partial nephrectomy, and recovery of disturbed renal function is imperative post partial nephrectomy. We previously have demonstrated the decellularized (DC) scaffolds could mediate the residual kidney regeneration and thus improve disturbed renal function after partial nephrectomy. However, the cellular changes including the angiogenesis in the implanted DC scaffold has not yet been elaborated. In this study, we observed that the scaffold promoted the proliferation of human umbilical vein endothelial cells (HUVEC) that adhered to the DC scaffold in vitro. We next examined the pathological changes of the implanted DC graft in vivo, and found a decreased volume of the scaffold and a dramatic angiogenesis within the scaffold. The average microvessel density (aMVD) increased at the early stage, while decreased at the later stage post transplantation. Expression level of vascular endothelial growth factor (VEGF) showed similar dynamic changes. In addition, many endothelial cells (ECs) and endothelial progenitor cells (EPCs) were distributed in the region which contained active angiogenesis in the scaffold. However, the implanted graft became fibrosis and the angiogenesis degraded at final stage roughly 8 weeks post transplantation. Our data indicate that DC scaffold can be vascularized in vivo and possible mechanisms are discussed.