In a recent study featured in Cell Stem Cell, researchers from USC have made notable advancements in the cultivation of nephron progenitor cells (NPCs), which are responsible for forming the kidney’s filtration system. NPCs have great potential for gaining insights into kidney development, simulating diseases, and uncovering new treatments. The team has enhanced the chemical combination used to generate and grow NPCs in the lab, allowing for the sustained growth of both mouse and human NPCs in a simple 2-dimensional format.The nephrons are destined to develop the kidney’s filtration system. NPCs have great potential for improving our understanding of kidney development, modeling diseases, and finding new treatments. “By enhancing our ability to grow NPCs from human stem cells, we create a new way to understand and fight congenital kidney diseases and cancer,” said Zhongwei Li, an assistant professor of medicine and stem cell biology at the Keck School of Medicine of USC and the lead author of the study. The National Institutes of Health partially funded the research, which was conducted by the Li Lab postdocs Biao Huang and Zipeng.Zeng and their team have enhanced the chemical mixture used for creating and cultivating NPCs in the lab. This improved cocktail allows for the continuous growth of both mouse and human NPCs in a more straightforward 2-dimensional format. This is a significant advancement from the previous 3-dimensional system, which was not only more complicated but also limited the ability to conduct genome editing on the cells.
Furthermore, the cocktail also facilitates the expansion of induced NPCs (iNPCs) from human pluripotent stem cells. These iNPCs closely resemble native human NPCs. With this method, iNPCs can be produced from any individual starting with a simple b.A blood or skin biopsy will be used to assist in developing personalized kidney disease models and improving the search for drugs targeting the nephron. Additionally, the combination is potent enough to transform a specialized kidney cell, called a podocyte, into an NPC-like state.
To showcase the real-world benefits of their discovery, the researchers edited the genomes of the NPCs to identify genes linked to kidney disease and development. This screening revealed both known and new genes with potential implications.Scientists have inserted the genetic mutations that cause polycystic kidney disease (PKD) into NPCs. These NPCs grew into small kidney structures called organoids, which showed cysts, a key symptom of PKD. The team then used the organoids to search for drug-like substances that could stop cyst formation.
“This advancement could greatly impact kidney research in various ways, from speeding up drug discovery to uncovering the genetic basis of kidney development, disease, and cancer,” said Li. “Furthermore, it also offers a supply of NPCs as essential components for creating artificial kidneys.”r kidney replacement therapy.”
80% of the funding for this research was provided by the National Institutes of Health (NIH) through grants DK054364, T32HD060549, and DP2DK135739 from the NIH Common Fund’s High-Risk High-Reward Research program. The University Kidney Research Organization (UKRO) also provided additional support, along with funding from a Keck School of Medicine of USC Dean’s Pilot Award, a USC Stem Cell Challenge Grant, a USC Provost’s Undergrad Research Fellowship, a Chan Zuckerberg Initiative seed network grant (CZIF2019-002430), and a CIRM Bridges Award.
McMahon provides scientific advice and consulting for this work.Li, Huang, Zeng, McMahon, Hallows, and Pastor-Soler are inventors for Novartis, eGENESIS, Trestle Biotherapeutics, GentiBio, and IVIVA Medical. The technologies described in this study have had intellectual property protection applied for by these individuals.
