The urologic application of human pluripotent stem cells (hPSCs): Differentiation of hPSCs into nephron progenitor cells and bladder urothelium

Abstract

Part I. Differentiation of Human Pluripotent Stem Cells into Bipotent Nephron Progenitor Cells in a Serum and Feeder Free System Kidney disease is emerging as a critical medical problem worldwide. Because of limited treatment options for the damaged kidney, stem cell treatment is becoming an alternative therapeutic approach. Of many possible human stem cell sources, pluripotent stem cells are most attractive due to their self-renewal and pluripotent capacity. However, little is known about the derivation of renal lineage cells from human pluripotent stem cells (hPSCs). In this study, I developed a novel protocol for differentiation of nephron progenitor cells (NPCs) from hPSCs in a chemically defined serum- and feeder-free system. I designed step-wise protocol for differentiation of human pluripotent stem cells toward primitive streak, intermediate mesoderm and NPCs by recapitulating normal nephrogenesis. After modification of culture period and concentration of exogenous factors, hPSCs can differentiate into NPCs that markedly expressed specific marker genes such as SIX2, WT1, PAX2 and SALL1 in transcription and protein levels. Moreover, NPCs possess the potential of bidirectional differentiation into both renal tubular epithelial cells and glomerular podocytes in defined culture conditions. They can also form in vitro tubule-like structures in three dimensional culture systems. Thus, this novel protocol for hPSCs differentiation into NPCs can be useful for producing alternative sources of cell replacement therapy and disease modeling for human kidney diseases.

Part II. Directed Differentiation of Human Pluripotent Stem Cells into Bladder Urothelium in a Serum and Feeder Free System Human stem cells have been considered promising cell sources for bladder regeneration. Among several possible sources of human stem cells, pluripotent stem cells are most fascinating because they can differentiate into any of the cell types in the body and exhibit unlimited proli...