Vascularized Bioengineered Kidney Using Decellularized Scaffold Recellularized with human Placenta-Derived Angiogenic stem Cells and Kidney Organoids

Abstract

A bioengineered kidney using a decellularized kidney scaffold (DKS) offers a promising solution to the kidney shortage. However, the transplantation of bioengineered kidneys using DKS recellularized with human endothelial, renal cells or others has not yet successfully achieved the vascular and renal reconstruction in vivo. In this study, we identified another type of stem cells, designated as human placenta-derived angiogenic stem cells (hPASCs), which serve as seeding cells for the vascularization of DKS. These hPASCs encompass angiogenic subpopulations, exhibit both stem cell properties and the capacity for vascular differentiation. Human fetal kidney organoids (KIO) were established as a source of renal parenchymal cells, comprising renal, immune, and vascular cell populations. We developed a vascularized bioengineered kidney by recellularizing DKS with hPASCs and KIO using a circulation perfusion culture system. The hPASCs bioengineered kidney demonstrated enhanced angiogenesis and reconstructed renal architecture in vivo, by transplantation into rat models of renal subcapsular and partial nephrectomy. Furthermore, immunofluorescence and single-cell analyses revealed that the hPASCs revascularized bioengineered kidney regenerated both vascular and renal parenchymal cells within the host. This study offers another strategy for kidney bioengineering and regeneration.