Obstacles in Renal Regenerative Medicine: Metabolic and Epigenetic Parallels Between Cellular Reprogramming and Kidney Cancer Oncogenesis

Context: Regenerative medicine has recently presented a revolutionary solution to end-stage kidney disease. Reprogramming patients' own cells generates induced pluripotent stem cells that are subsequently differentiated to "kidney organoid," a structure that is anatomically and functionally similar to the kidney. This approach holds the promise of a transplantable, immunocompetent, and functional kidney that could be produced in vitro. However, caution must be taken due to the molecular-level similarities between induced pluripotent stem cells and renal cell carcinomas. As such, if cell reprogramming is not tightly controlled, it can lead to carcinogenic changes.

Objective: Based on recent next-generation sequencing results and other supporting data, we identified three major molecular attributes of renal cell carcinoma: metabolic alterations, epigenetic changes, and miRNA-based alterations. Strikingly, these variations are mirrored in induced pluripotent stem cells, which are the main cell source of renal regenerative medicine. Our objective was to discuss the shared metabolic, epigenetic and miRNA-regulated characteristics and to abridge their significance in renal regenerative medicine.

Evidence acquisition: English-language literature was retrieved through PubMed.

Evidence synthesis: Authors collected the published evidence and evaluated the content based on independent literature findings. Articles were filtered to include only highly relevant, recent publications that presented reproducible results by authorities of the field.

Conclusions: The kidney represents a unique metabolic environment that could be hijacked by induced pluripotent stem cells or by partially differentiated cells for oncogenic transformation. Future differentiation protocols must produce kidney organoids that are fully engaged in filtration function.

Patient summary: A new technology can produce mini-kidneys or kidney organoids. This review discusses some of the challenges this technology has to face, including its high oncogenic potential. Understanding these similarities will lead to the safe creation of new functional kidney units in patients with kidney failure.