In a new study published in Cell Stem Cell, USC scientists have made significant advancements in cultivating nephron progenitor cells (NPCs), which are essential in the formation of the kidney’s filtration system, the nephrons. These cells have great potential for understanding kidney development, modeling diseases, and discovering new treatments. Lead author Zhongwei Li and his team improved the chemical cocktail used to generate and grow NPCs in the laboratory, enabling sustained growth of both mouse and human NPCs in a simple 2-dimensional format. This new approach allows for genome editing on the cells and the expansion of induced NPCs from human pluripotent stem cells, facilitating the creation of patient-specific kidney disease models.
The improved cocktail developed by Li’s team also allows for the reprogramming of a differentiated kidney cell known as a podocyte into an NPC-like state. By introducing genetic mutations responsible for polycystic kidney disease (PKD) into the NPCs, the scientists were able to generate mini-kidney structures, or organoids, that exhibited cysts, a characteristic symptom of PKD. These organoids were then used to screen for drug-like compounds that inhibit cyst formation. Li believes that this breakthrough has the potential to advance kidney research in various critical areas, from speeding up drug discovery to uncovering the genetic basis of kidney development, diseases, and cancer, ultimately providing essential supplies of NPCs for building synthetic kidneys for kidney replacement therapy.
The study was funded in part by the National Institutes of Health, with additional support from various organizations, including the University Kidney Research Organization (UKRO) foundation and the Chan Zuckerberg Initiative. Michael McMahon, one of the researchers involved in the study, has disclosed affiliations with pharmaceutical and biotech companies, but Li and his team have applied for intellectual property protection for the technologies described in the study. By harnessing the power of NPCs and their ability to model kidney diseases and development, Li’s team has opened up new possibilities for improving treatments and understanding the complex processes involved in kidney health.
The ability to generate iNPCs from any individual starting with a simple blood or skin biopsy allows for the creation of personalized kidney disease models, enhancing efforts to identify nephron-targeted drugs. The team also demonstrated the practical applications of their research by performing genome editing on the NPCs to identify genes related to kidney development and disease, uncovering both known and novel candidates. By successfully creating organoids that mimic PKD symptoms, the scientists have highlighted the potential of their breakthrough in advancing kidney research and providing important resources for kidney replacement therapy.
The breakthrough made by Li and his team has the potential to revolutionize kidney research by providing a platform for accelerating drug discovery, uncovering the genetic factors underlying kidney diseases, and building synthetic kidneys for replacement therapy. The funding received from various sources, including the National Institutes of Health, has supported the critical work carried out by the researchers. By enhancing our understanding of kidney development and disease modeling, this research has opened up new avenues for combatting congenital kidney diseases, cancer, and other disorders that affect kidney health. The innovative approach developed by Li’s team represents a significant step forward in harnessing the potential of NPCs for improving treatments and outcomes for individuals with kidney-related conditions.
