Scientists have solved a medical mystery in a rare, poorly understood disease by uncovering which cells cause tumors in patients with tuberous sclerosis complex (TSC). They did this by creating genetically engineered kidney organoids, or “mini-kidneys” grown from human tissue, as described in a pape
“The cells at the origin of tuberous sclerosis tumors have been a mystery for decades,” said senior author Dr. Bill Stanford, senior scientist at The Ottawa Hospital and professor at the University of Ottawa. “Our results can help find possible treatment targets for this challenging disease.”
“Kidney disease is the leading cause of death in patients with TSC. Around 60 to 80 percent of patients develop tumors in their kidneys, often reducing kidney function and sometimes leading to catastrophic bleeding,” said lead Dr. Adam Pietrobon, MD-PhD student at The Ottawa Hospital and the University of Ottawa. “There were no adequate lab models to study how TSC affects the kidney, so we made one ourselves.
TSC tumors in the kidney have baffled experts because they are incredibly diverse in size, cellular makeup, and gene expression, even within the same patient. What causes this wide diversity was unknown, and it makes treatment challenging. Using these organoids, the scientists revealed that cells called Schwann Cell Precursors are where TSC tumors start in the kidney. They also discovered this single mutation affects the development of many different kinds of cells, which explains the variation in kidney tumors even within the same person.
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