OTTAWA, Ontario — Tiny lab-grown kidneys have helped scientists discover the cause of a mysterious genetic disease.
Researchers in Canada say they have used these genetically engineered kidney organoids (or “mini-kidneys”) to find out what causes patients with tuberous sclerosis complex (TSC) to develop tumors throughout their bodies. TSC is a rare condition that causes benign tumors to grow in the skin, brain, kidneys, heart, and lungs.
TSC tumors are also very diverse and develop in children or adults. These patients have a range of symptoms, from mild to life-threatening, including seizures and kidney failure. Currently, there is no cure for TSC.
“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, said in a press release. “Our results may help identify potential treatment targets for this challenging disease.”
“Kidney disease is the leading cause of death in patients with TSC. About 60 to 80 percent of patients develop tumors in their kidneys, which often impair kidney function and sometimes lead to catastrophic bleeding,” adds lead adr. 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 kidneys, so we made our own.”
A single genetic mutation is to blame
Researchers say that TSC is the result of a mutation in the TSC1 or TSC2 gene. Most patients see this mutation develop naturally during childhood rather than inheriting it from a parent. This actually makes it harder for scientists to study. Moreover, there are no animal models that fully capture the impact of TSC on human kidneys.
The tumors in the kidneys were a mystery to researchers because of their diversity in size, cellular composition and gene expression. Doctors even see differences between multiple tumors in a single patient.
To find out what makes the tumors so diverse, the researchers grew their own 3D kidney tissue in a lab from human stem cells. The mini kidneys are also genetically engineered to have a TSC1 or TSC2 mutation. Simply put, organoids are miniature versions of organs that scientists grow artificially. In this case, the lab-grown kidneys had the same genetic profile as someone with TSC tumors.
The study authors took individual cells from the kidney organoids and injected them into the kidneys of mice. The cells grew into human TSC tumors.
Through this process, the team discovered that special cells called Schwann Cell Precursors are where TSC tumors develop in the kidney. In addition, this single mutation affects the development of different types of cells in the body. Researchers say this finally explains why the disease causes so many different types of tumors in a single patient.
“These ‘mini-kidneys’ can not only help us better understand this disease, they could also be used to test new therapies,” concludes Dr. Pietrobon.
The study is published in the journal Mobile Reports†