Researchers have solved a medical mystery in a poorly understood disease by uncovering which cells cause tumors in patients with tuberous sclerosis complex (TSC). As described in the journal Cell Reports, they did this by creating genetically engineered kidney organoids, or "mini-kidneys" grown from human tissue.
"The cells at the origin of tuberous sclerosis tumors have been a mystery for decades. Our results can help find possible treatment targets for this challenging disease," said senior author Dr. Bill Stanford from the Ottawa Hospital.
TSC is a rare genetic disease that causes benign tumors in the skin, brain, kidneys, heart or lungs. TSC tumors are very diverse, arising in children or adults with a range of symptoms from mild to life-threatening. There is no cure and treatment options are limited.
Kidney disease is the leading cause of death in patients with TSC. The disease often reduces kidney function and sometimes leads to catastrophic bleeding. Co-author Dr. Adam Pietrobon from the Ottawa Hospital and the University of Ottawa says: "There were no adequate lab models to study how TSC affects the kidney, so we made one ourselves."
TSC is caused by mutations in the TSC1 or TSC2 gene. For most patients, these mutations arise spontaneously during development or early life rather than being inherited from their parents. This makes TSC a difficult disease to study.
While lab researchers often use animals to study human diseases, there was no animal model that fully captured TSC's impact on the kidneys.
Known as organoids, these miniature, simplified versions of kidneys had a genetic profile similar to TSC tumors found in patients. The researchers then took single cells from these kidney organoids and injected them into the kidneys of mice, where they grew into human TSC tumors.
Using these organoids, the researchers revealed that cells called Schwann Cell Precursors are where TSC tumors start in the kidney. Not only can these 'mini-kidneys' help better understand this disease, but they can also be used to test new therapies.
