PhD defence A.S. (Anusha) Shankar

Summary: Kidney transplantation is the optimal treatment for patients with kidney failure. However, there is a persistent organ shortage and there are no alternative treatments besides dialysis and conservative treatment. Induced pluripotent stem cells can be used to generate three dimensional kidney structures called kidney organoids. They may potentially be able to replace non-functional or injured kidney tissue. However, not much is known about their function and stability. The objective of our research was to study the potential of kidney organoids in regenerative therapy and to examine the robustness of the model, functionality, and safety. Firstly, we developed an efficient method to quantify variability in the generation of kidney organoids, which may aid in improving the robustness of protocol. We also discovered the ability of kidney organoids to produce renin, an enzyme that plays a role in regulating blood pressure. Moreover, we found that organoids were able to convert inactive vitamin D to its active form. In order to analyze their long-term stability, we implanted kidney organoids in a mouse model and found that kidney organoids have the ability to form tumors. Therefore, it may be important to consider evaluation of tumorigenicity in kidney organoids prior to their clinical implementation. Finally, we studied their interaction with the human immune system and developed a model for transplant-related kidney injury. All in all, we have discovered several novel attributes of kidney organoids essential to their applicability and which will advance the utility of kidney organoids for regenerative medicine.