Credit: Biao Huang/Li LabResearchers at USC have advanced kidney research by developing a brand-new method to cultivate nephron progenitor cells from human stem cells. This approach simplifies the process and boosts applications in disease modeling and drug discovery.In a brand-new research study released today in Cell Stem Cell, USC scientists report considerable development in cultivating nephron progenitor cells (NPCs), the cells destined to form the kidneys purification system, the nephrons.”By improving our ability to grow NPCs from human stem cells, we produce a new opportunity for understanding and combating genetic kidney illness and cancer,” said matching and lead author Zhongwei Li, an assistant professor of medicine, and stem cell biology and regenerative medication at the Keck School of Medicine of USC.In the research study, moneyed in part by the National Institutes of Health, Li Lab postdocs Biao Huang and Zipeng Zeng and their partners enhanced the chemical mixed drink for producing and growing NPCs in the laboratory.This improved cocktail allows the continual growth of both mouse and human NPCs in an easy 2-dimensional format.
Lab-grown human nephron progenitor cells. Credit: Biao Huang/Li LabResearchers at USC have actually advanced kidney research study by establishing a new technique to cultivate nephron progenitor cells from human stem cells. This technique streamlines the procedure and improves applications in disease modeling and drug discovery.In a new study published today in Cell Stem Cell, USC scientists report considerable progress in cultivating nephron progenitor cells (NPCs), the cells predestined to form the kidneys filtering system, the nephrons. NPCs hold enormous guarantee for comprehending kidney advancement, modeling diseases, and finding new treatments.”By boosting our ability to grow NPCs from human stem cells, we develop a new opportunity for understanding and combating genetic kidney illness and cancer,” said corresponding and lead author Zhongwei Li, an assistant professor of medicine, and stem cell biology and regenerative medicine at the Keck School of Medicine of USC.In the study, funded in part by the National Institutes of Health, Li Lab postdocs Biao Huang and Zipeng Zeng and their collaborators improved the chemical mixed drink for producing and growing NPCs in the laboratory.This improved cocktail allows the continual growth of both mouse and human NPCs in a basic 2-dimensional format. This marks a major enhancement over the previous 3-dimensional system, which was not only more troublesome, but also restricted the ability to carry out genome modifying on the cells.The cocktail likewise enables the expansion of caused NPCs (iNPCs) from human pluripotent stem cells. These iNPCs carefully look like native human NPCs. With this technique, iNPCs can be produced from any individual beginning with a simple blood or skin biopsy. This method will assist in the development of patient-specific kidney disease designs and improve efforts to identify nephron targeted drugs.Moreover, the mixed drink is powerful enough to reprogram a separated kind of kidney cell called a podocyte into an NPC-like state.Demonstrating the practical applications of their advancement, the scientists performed genome editing on the NPCs to evaluate for genes connected to kidney advancement and disease. This screening determined formerly implicated genes, along with novel candidates.In a more presentation, the scientists introduced the genetic anomalies accountable for polycystic kidney disease (PKD) into the NPCs. These NPCs developed into mini-kidney structures, understood as organoids, displaying cysts– the hallmark symptom of PKD. The group then utilized the organoids to evaluate for drug-like compounds that prevented cyst development.”This development has possible for advancing kidney research in numerous critical ways– from accelerating drug discovery to deciphering the hereditary underpinnings of kidney cancer, disease, and advancement,” stated Li. “Importantly, it also offers materials of NPCs as vital foundation to develop artificial kidneys for kidney replacement therapy.”Reference: 30 April 2024, Cell Stem Cell.Additional co-authors consist of: Sunghyun Kim, Connor C. Fausto, Kari Koppitch, Hui Li, Xi Chen, Jinjin Guo, Chennan C. Zhang, Tianyi Ma, Pedro Medina, Megan E. Schreiber, Mateo W. Xia, Ariel C. Vonk, Tianyuan Xiang, Tadrushi Patel, Yidan Li, Riana K. Parvez, Jyun Hao Chen, Matthew E. Thornton, Brendan H. Grubbs, Yali Dou, Ksenia Gnedeva, Qi-Long Ying, Nuria M. Pastor-Soler, Kenneth R. Hallows, Nils O. Lindström, and Andy McMahon from USC; Zexu Li and Teng Fei from Northeastern University in Shenyang, China; Balint Der from USC and Semmelweis University in Budapest, Hungary; Zhenqing Liu from City of Hope; and Yarui Diao from the Duke University School of Medicine.Eighty percent of this work was supported by federal funding from the National Institutes of Health (NIH) (grant numbers DK054364, and T32HD060549) and the NIH Common Funds High-Risk High-Reward Research program (grant number DP2DK135739). Additional support came from University Kidney Research Organization (UKRO) structure funding, a Keck School of Medicine of USC Deans Pilot Award, a USC Stem Cell Challenge Grant, a USC Provosts Undergrad Research Fellowship, a Chan Zuckerberg Initiative seed network grant (CZIF2019-002430), and a CIRM Bridges Award.McMahon is a clinical advisor or consultant for Novartis, eGENESIS, Trestle Biotherapeutics, GentiBio, and IVIVA Medical. Li, Huang, Zeng, McMahon, Hallows, and Pastor-Soler have looked for copyright protection for innovations explained in this study.