Study of the Week: Research Using “Mini-Kidneys” Leads to Tuberous Sclerosis Complex Discovery

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

Renal organoid modeling of tuberous sclerosis complex reveals lesion features arise from diverse developmental processes

We previously published about this research in a story titled “Researchers Created Mini-Kidneys to Identify Tuberous Sclerosis Complex and Solve a Medical Mystery” which can be found here. The study was originally published in the scientific journal Cell Reports. You can read the full text of the study here

This research team was affiliated with the University of Ottawa.

What Happened?

Tuberous sclerosis complex (TSC) is a disorder caused by the loss of the TSC1 or TSC2 genes and leads to the formation of tumors in various parts of the body. In the kidneys, angiomyolipomas and cysts are common. However, scientists still don’t understand from which cells that these tumors originate. In this study, researchers sought to finally solve this mystery. In the kidneys in particular, tumors in this disorder have remarkable diversity in size, gene expression, and cellular makeup, making them very puzzling to researchers.

In order to conduct this precise research, the scientists decided to develop kidney organoids to use as a model. This was conducted in a laboratory setting and involved cultivating 3D kidney tissue using human stem cells. These cells were engineered to have mutations in the TSC1 or TSC2 genes in order to model tuberous sclerosis complex. Single cells from these organoids were then inserted into the kidneys of mice. They started developing into human TSC tumors.

The scientists ultimately found that cells called Schwann cell precursors are the origin of tuberous sclerosis tumors in the kidneys. Furthermore, the mutations in the disease impact several different types of cells. This helps explain the great variation in kidney tumors seen in different patients and even within the same patient. 

Overall, these findings help further the understanding of tuberous sclerosis complex. Furthermore, the successful development of tuberous sclerosis complex kidney organoids is notable as well, since they could be used to test new potential therapies for the disorder.

About Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a rare genetic disease that causes a variety of symptoms. It is most distinguished by the appearance of non-cancerous tumors, which grow in the brain, lungs, eyes, liver, skin, and other organs. The disease is triggered by mutations affecting the TSC1 or TSC2 genes, which code for proteins that normally suppress the appearance of tumors. Tuberous sclerosis complex can inflict a variety of symptoms, such as intellectual disability, skin changes, disease affecting the lungs or kidneys, behavioral abnormalities, developmental delays, autism, and seizures. The broad systemic impacts of the disease require frequent management and monitoring of tumors; a variety of specialist expertise may be necessary. Outcomes vary, but with good management most patients have a normal life expectancy. Many patients with mild symptoms remain undiagnosed. To learn more about tuberous sclerosis complex, click here.

Why Does it Matter?

The findings from this study are vital for understanding the origin of kidney tumors in tuberous sclerosis complex. While generally not particularly dangerous, tumors of the kidney in the disease can cause blood to appear in the urine, and when they grow larger, the risk of severe bleeding is also increased. The majority of patients, up to 80 percent, will develop kidney tumors. In addition, kidney disease is the leading cause of death in tuberous sclerosis complex:

“Around 60 to 80 percent of patients develop tumors in their kidneys, often reducing kidney function and sometimes leading to catastrophic bleeding. There were no adequate lab models to study how TSC affects the kidney, so we made one ourselves.” – Dr. Adam Pietrobon, MD-PhD student, The Ottawa Hospital and the University of Ottawa

“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.” – Dr. Bill Stanford, senior author, senior scientist, The Ottawa Hospital, professor, the University of Ottawa

With the kidney being an area of special concern in this disease, these findings are an important stepping stone to the development of therapies that can reduce the impacts of tuberous sclerosis tumors on the function of the kidney, and therefore the health of patients living with the disease overall. 

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