Tuberous Sclerosis Complex (TSC) is an incurable genetic disease that causes tumor formation in various organs. In the kidney, the growth of renal angiomyolipomas (AMLs) can lead to loss of renal function and premature death caused by the spontaneous rupture of vascular aneurysms. For the last three decades, our understanding of AML biology has been greatly limited by the lack of appropriate experimental models. However, in a new paper published in Nature Communications, researchers from the lab of Dario Lemos, HSCI Affiliate Faculty, report a landmark bioengineering method for modelling the renal manifestations of this rare disease, laying the groundwork for the testing of new therapies.

Titled, “A Tissue-Bioengineering Strategy for Modeling Rare Human Kidney Diseases In Vivo," the paper documents the use of renal organoids generated from patient-derived induced pluripotent stem cells (iPSCs), somatic cells that can be differentiated into many types of tissue, taken from TSC patients. Transplanting these organoids into immunodeficient rats allowed the researchers to investigate the mechanisms driving kidney lesions, such as AML.

With the organoids, the research team was able to identify a mechanism of tumor resistance and to test locally-delivered drug-loaded nanoparticles as a treatment for AML. These nanoparticles delivered near the grafts rapidly shrank the organoids without affecting the healthy kidney, improving upon current treatments, which only partially shrink kidney AMLs in TSC patients, often requiring life-long treatment as a result.

“Our new human AML organoid transplant model is an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo,” said Dario Lemos, PhD, an assistant professor at Harvard Medical School and a principal investigator in the Brigham’s Renal Division. “We expect that this model may become a widely-used experimental platform for the study of disease mechanisms and for the development of new therapies targeting these tumors.”