Isolation and long-term expansion of a single adult human renal epithelial cell with efficient kidney regeneration capacity

Abstract

A wide spectrum of lethal kidney diseases involves the irreversible destruction of the tubular structures which leads to loss of renal function. A reliable technological platform to culture and transplant adult human-derived cells with nephrogenic potential offers great hope to facilitate human kidney regeneration. Here, we show that in an appropriate feeder cell-based culture system, it is feasible to isolate and long-term expand the progenitor-like SOX9+ renal epithelial cells (SOX9+ RECs) from adult mammalians. Single cell-derived SOX9+ REC lines can be established from human needle biopsy or urine samples with molecular homogeneity and genomic stability maintained during culture. Such cells grown in 3D culture system could self-organize into renal organoids composed of proximal tubular, Loop of Henle (LOH) and distal tubular cells as illustrated by single cell transcriptomic analysis. Once being transplanted into the physically injured mouse kidney, the expanded single human SOX9+ RECs incorporated into the damaged area and demonstrated capacity of regenerating functional tubules in vivo. Altogether, the ability to extensively propagate human SOX9+ REC in culture whilst concomitantly maintaining their intrinsic lineage differentiation commitment suggests their future application in regenerative medicine.