A thorough investigation into the differences between mice and human kidneys may lead to new classes of drugs and better treatment options.
Researchers from the University of Southern California have built a free online kidney atlas that empowers stem cell scientists to generate more human-like tiny kidneys for testing new drugs and creating renal replacement therapies.
“Stem-cell based technologies hold great promise for developing kidney replacement and regeneration therapies,” Nils Lindstrom, first author of three new studies and a research associate in Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, said in a statement. “Getting there requires detailed knowledge of how kidneys normally form so the process can be replicated in cell cultures in the lab.
“Our data will help us and other scientists improve current techniques to make better tiny functional kidneys,” he added.
The researchers have documented the molecular, cellular and genetic similarities and differences between human and mouse kidney formation over the last four years. They also analyzed the developmental differences in scale, timing and basic structure between human and mouse kidneys. They gained insight into the regulatory processes that maintain, expand and turn kidney stem cells into mature, functional kidney structures by examining human kidneys at different stages of development and juxtaposing their observations with mouse kidneys.
The team compared 26 human kidney anchor genes with their mouse equivalents and found that only three genes—SLC22A6, ENTPD5 and UMOD—have comparable expression between mouse and human kidneys.
“Our research bridges a critical gap between animal models and human applications,” Andrew McMahon, study senior author and W.M. Keck Provost Professor of Stem Cell Biology and Regenerative Medicine and Biological Sciences at the Keck School of Medicine, said in a statement. “The data we collected and analyzed creates a knowledge-base that will accelerate stem cell-based technologies to produce mini-kidneys that accurately represent human kidneys for biomedical screening and replacement therapies.”
“If the goal is to treat human kidney disease, clearly, it’s better to focus on genes that are also active in human kidneys,” McMahon said.
Carl Kesselman, study co-author and Dean’s Professor of Industrial and Systems Engineering at USC Viterbi, and his team at the Information Sciences Institute at USC Viterbi built software that automated many of the tasks researchers needed to perform, such as recording data observed by a high-resolution microscope.
The tool not only fast-tracked studies but also created an online, searchable library to help other stem cell scientists in their kidney disease research.
“If you think of data as the modern version of a book, we gave the researcher tools to write the book, made the library where the book is stored and created a catalog system so others can find the book and check it out,” Kesselman said.
Kidneys play a central role in controlling the body’s ecosystem by regulating blood pressure and removing waste products. The smallest functional unit that helps remove blood waste from the body are nephrons, which are formed in the human kidney only during fetal life, before the stem cells that generate them are exhausted.
Kidney disease affects about 30 million in the U.S.
Filed Under: Drug Discovery