Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

TLDR

The scarcity of transplant allografts has spurred tissue‑regeneration efforts using seeded scaffolds, but the complexity of cell types and organ architecture limits progress. The study aimed to decellularize intact organs while preserving the matrix cues necessary for pluripotent cell differentiation. Intact rat kidneys were decellularized to retain their intricate architecture and seeded with murine embryonic stem cells either antegrade through the artery or retrograde through the ureter. Primitive precursor cells proliferated in glomerular, vascular, and tubular structures, lost their embryonic appearance while expressing differentiation markers, and cells lacking basement‑membrane contact underwent apoptosis to form lumens, indicating that the extracellular matrix directs kidney regeneration and that seeded scaffolds can reveal differentiation pathways.

Abstract

The scarcity of transplant allografts for diseased organs has prompted efforts at tissue regeneration using seeded scaffolds, an approach hampered by the enormity of cell types and complex architectures. Our goal was to decellularize intact organs in a manner that retained the matrix signal for differentiating pluripotent cells. We decellularized intact rat kidneys in a manner that preserved the intricate architecture and seeded them with pluripotent murine embryonic stem cells antegrade through the artery or retrograde through the ureter. Primitive precursor cells populated and proliferated within the glomerular, vascular, and tubular structures. Cells lost their embryonic appearance and expressed immunohistochemical markers for differentiation. Cells not in contact with the basement membrane matrix became apoptotic, thereby forming lumens. These observations suggest that the extracellular matrix can direct regeneration of the kidney, and studies using seeded scaffolds may help define differentiation pathways.