The immunogenicity of human kidney organoids

Safety issues of human iPSC-derived kidney organoids as a regenerative therapy need to be evaluated. Therefore, we studied the immunogenicity of human iPSC-derived kidney organoids. We subcutaneously implanted kidney organoids in immune-deficient IL2Ry-/-RAG2-/- mice for 1 month and hereafter performed adoptive transfer of healthy allogeneic human PBMC. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of kidney organoid cells and immune cell profiles. We investigated whether innate and adaptive immune cells invade kidney organoids, evoke an immune response, and influence the kidney organoid differentiation and functional capacity. Understanding the immunogenicity of kidney organoids will advance studies in the applicability of kidney organoids for regenerative medicine. Furthermore, it can serve as an in-vivo transplantation model to study solid organ transplantation. Kidney organoids were harvested in-vivo from mice as described in the methods (two months after implantations and four weeks after human PBMC administration). Organoids were digested by TrypLE Select and stored in ice until sequencing. Control samples (Sample 1-3) are from kidney organoids that were subcutaneosly implanted in mice for 2 month. Samples 4-7 (PBMC 1-4) correspond to kidney organoids subcutaneosly implanted and that had an adoptive transfer of healthy allogenic human PBMC (via intraperitoneal injection).