How tuberous sclerosis occurs
"Mini-kidneys" grown in the laboratory helped to study a rare disease
Tatiana Matveeva, "Scientific Russia" (https://scientificrussia.ru /)
Canadian scientists have grown genetically modified kidney organoids from human tissues and with their help found out which cells cause tumors in patients with tuberous sclerosis, reports EurekAlert!. The scientists' findings are presented in the journal Cell Reports (Renal organoid modeling of tubular sclerosis complex reveals lesion features arise from diverse developmental processes).
"The cells in the origin of tuberous sclerosis tumors have been a mystery for decades," said senior study author Dr. Bill Stanford, a senior researcher at the Ottawa Hospital and a professor at the University of Ottawa. "Our results may help to find possible treatment targets for this complex disease."
Tuberous sclerosis (TS) is a rare genetic disease that causes benign tumors in the skin, brain, kidneys, heart or lungs. Tumors are very diverse, occur in children or adults with a range of symptoms from mild to life-threatening and often include seizures and kidney problems.
TS occurs due to mutations in the TSC1 or TSC2 gene. In most patients, these mutations appear spontaneously during development or at an early age, and are not inherited from parents. This creates difficulties for the study of tuberous sclerosis. TS tumors in the kidneys are extremely diverse in size, cellular composition and gene expression, even in the same patient. The reasons for this diversity are unknown.
To better understand the effect of this disease on the kidneys, the team grew three-dimensional kidney tissue in the laboratory from human stem cells that were genetically engineered to carry TSC1 or TSC2 mutations. The genetic profile of these miniature organoids was similar to TS tumors. The researchers then took individual cells from these renal organoids and injected them into the kidneys of mice, where they "turned" into human tumors.
Using these organoids, the researchers found that the precursor cells of Schwann cells are the place where the TS tumor begins to develop. It turned out that this single mutation affects the development of many different cell types, which explains the differences in kidney tumors even in the same person.
"Mini-kidneys" not only allow us to better understand the disease – they can also be used to test new treatments, the authors of the work note.
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