Exploring immune response toward transplanted human kidney tissues assembled from organoid building blocks

The increasing scarcity of organs and the significant morbidity linked to dialysis require the development of engineered kidney tissues from human-induced pluripotent stem cells. Integrative approaches that synergize scalable kidney organoid differentiation, tissue biomanufacturing, and comprehensive assessment of their immune response and host integration are essential to accomplish this. Here, we create engineered human kidney tissues composed of organoid building blocks (OBBs) and transplant them into mice reconstituted with allogeneic human immune cells. Tissue-infiltrating human immune cells are composed of effector T cells and innate cells. This immune infiltration leads to kidney tissue injury characterized by reduced microvasculature, enhanced kidney cell apoptosis, and an inflammatory gene signature comparable to kidney organ transplant rejection in humans. Upon treatment with the immunosuppressive agent rapamycin, the induced immune response is greatly suppressed. Our model is a translational platform to study engineered kidney tissue immunogenicity and develop therapeutic targets for kidney rejection. [Display omitted] •Like human transplants, engineered iPSCs-derived kidney tissues face immune rejection•Immune infiltration causes microvascular injury and cell death in humanized mouse model•Engineered kidney tissues mimic rejection and aid in testing immunosuppressive drugs•Rapamycin prevents rejection and preserves the integrity of transplanted kidney tissues Health sciences; Immunology; Bioengineering; Tissue engineering