Erythropoietin delivery through kidney organoids engineered with an episomal DNA vector

• Kidney organoids derived from iPSCs can be engineered with a non-integrating S/MAR DNA vector to stably overexpress erythropoietin (EPO), enabling sustained EPO delivery. • Implantation of EPO-overexpressing kidney organoids into immunodeficient mice significantly elevated hematocrit levels in a dose-dependent manner, demonstrating functional systemic effects. • EPO+ organoids also influenced bone homeostasis, evidenced by altered trabecular bone composition, suggesting broader therapeutic implications beyond anemia correction. • This approach offers a promising regenerative strategy for restoring endocrine kidney function, potentially overcoming limitations of current EPO supplementation therapies.