Human nephron progenitors and renal specification
Most kidney diseases leading to End Stage Renal Disease (ESRD) originate when podocytes, the key cells in maintenance of the glomerular structure and function, are lost. Kidney failure can become irreversible because podocytes cannot be replaced, since they have very limited regenerative capability. Very little is known about the origin of renal cell progenitors, about the development of podocytes during the embryonic phase and it is also unclear which are the major important signaling pathways that regulate human kidney development. There are no in vitro systems that can be used in order to study the biology of kidney progenitor cells as well as the specification of podocytes. Therefore, a new culture system that will allow kidney progenitors to be propagated, not only maintaining their self-renewal, but that can also be induced to become fully mature kidney cells, is needed. We have identified a novel kidney progenitor population within the amniotic fluid (hAKPC-P) that expresses markers of embryonic kidney cells and that under specific conditions can be differentiated into podocytes. In this project we propose to study how self-renewal and kidney specification is regulated in hAKPC-P. In conclusion, we believe that hAKPC-P will help to elucidate the biology of human kidney cells, in addition to understanding the causes of diseases resulting from loss and/or damage of kidney cells, like the podocytes.
The State of California is home to some of the nation's best kidney treatment centers. Having our laboratory next to one of California's busiest pediatric renal transplant programs we have been aware of the need for new and better alternative therapies to benefit our patients. In particular we focused our attention on chronic kidney disease, which is increasing every year. The kidneys, differently from other organs, possess limited regenerative capability, thus finding new stem cells/kidney progenitors that can substitute for damaged renal cells could make a significant impact in this field. These discoveries provide our child patients, as well as the adult patients in California, with alternative technologies that would benefit their longevity and quality of life. We have identified a new population of renal progenitors within the amniotic fluid, which can be easily obtained, stored, propagated and differentiated into renal cells, without genetic manipulation, thus eliminating some concerns over clinical compatibility and ethical concerns. In this study we intend to characterize these specific renal progenitor cells as a potential tool for understanding the molecular mechanisms that lead to renal differentiation. This knowledge will likely improve our understanding of common diseases resulting from loss and/or damage of renal cells. CIRM funding will ensure a competitive advantage for California in this innovative direction.