Culture Systems for Regenerative Kidney Therapy.

摘要

The long term goal of our work is to derive kidney tissue from embryonic stem cells. This will allow us to generate patientspecific models of polycystic kidney disease, which affects many military families. Self-renewal versus differentiation decisions of nephron progenitor cells are profoundly influenced by cells in their immediate environment, the so-called progenitor cell niche. The aim of our study was to recapitulate the progenitor cell niche in vitro to provide an environment for the propagation of nephron progenitor cells derived either from embryonic mouse kidneys or human embryonic stem cells. We have used a combinatorial screening approach to identify growth factors, small molecule inhibitors and extracellular matrix components that promote proliferation of undifferentiated nephron progenitor cells derived either from embryonic tissue or from human ES cells. Using these conditions we can accomplish approximately 1:4,000 expansion, resulting in billions of cells from a starting population of only a million. Importantly, our work shows that these cells not only maintain their undifferentiated phenotype, but also retain their capacity for differentiation to nephron tubules. Thus, we can now recapitulate human nephron development in vitro. This represents a very significant step forward and will form the foundation for the development of polycystic kidney disease models.