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Researchers Find New Method to Model Kidney Diseases
A doctor in a white lab coat and blue surgical face mask holds up their gloved hands. Between the hands is a graphic of two kidneys surrounded by a white glowing network.

Kidneys filter unwanted substances out of the blood and control the volumes of body fluids. They are made up of “nephrons,” the functional units of the kidney that develop from immature cells called nephron progenitor cells (NPCs). Scientists can grow NPCs in the lab to use as a model for kidney development and disease, but current methods for NPC care require tedious protocols to grow the cells long-term. These methods also don’t work easily with genetic screens that can identify genes associated with kidney diseases. NPCs can alternatively be grown from stem cells that have been derived from adult tissues like skin or blood, which offers scientists ways to study diseases and treatment methods in a patient-specific manner. However, it is difficult to maintain stem cell-derived NPCs in the lab with current methods. Dr. Zhongwei Li, a recipient of the NIH Common Fund’s High-Risk, High-Reward Research Program NIH Director’s New Innovator Award, developed a novel system to grow NPCs long-term that is compatible with stem cell-derived NPCs and can be used for genetic screening, disease modeling, and drug discovery.

Dr. Li and his team found a mixture of chemicals that allowed them to grow NPCs taken from both humans and mice more easily than existing methods. This mixture allowed them to generate and sustain NPCs derived from human stem cells, which could mature into nephron organoids (small organ-like collections of cells grown in the lab) that faithfully mimicked some functions of mature kidneys. The team used this new system to screen NPCs for genes implicated in cancer and congenital kidney diseases, some of which may provide new targets for potential therapies. The researchers further showed that their system could help understand and develop treatments for kidney diseases by modeling the development of kidney cysts resulting from a specific genetic mutation. Using their new NPC growth system, the researchers were able to test drugs that could prevent cyst formation and found thirteen effective drugs. With this new method to grow NPCs and model kidney development, Dr. Li and his team have opened new possibilities to understand kidney diseases and find treatments faster and more efficiently than ever before.

Reference: Huang B, Zeng Z, Kim S, Fausto CC, Koppitch K, Li H, Li Z, Chen X, Guo J, Zhang CC, Ma T, Medina P, Schreiber ME, Xia MW, Vonk AC, Xiang T, Patel T, Li Y, Parvez RK, Der B, Chen JH, Liu Z, Thornton ME, Grubbs BH, Diao Y, Dou Y, Gnedeva K, Ying Q, Pastor-Soler NM, Fei T, Hallows KR, Lindström NO, McMahon AP, Li Z. Long term expandable mouse and human induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease. Cell Stem Cell. 2024 April 30. doi:10.1016/j.stem.2024.04.002. Epub ahead of print. PMID: 38692273.

This page last reviewed on June 4, 2024