GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE263nnn/GSE263559/primaryOK200TranscriptomicsHomo sapiensExpression profiling by arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263559GEOGSEfalseNovel therapy for metabolic liver disease by transplantation of human iPS cell-derived 3D-organoidsUrea cycle dysbiosis—a severe metabolic liver disease caused by ornithine transcarbamylase (OTC) deficiency—is associated with hyperammonemia. Its only curative treatment is liver transplantation; however, severe shortage of organ donors poses a major challenge. Here, we report the generation of clinical-grade liver organoids from human induced pluripotent stem cells (hiPSC), which exhibit in vitro and in vivo ammonia metabolic functions. Quantitative metabolic flux analysis shows that the organoids have sufficient OTC enzyme activity and urea-producing function, implying their ammonia-metabolizing efficacy. The organoids show clear ameliorative effects on hyperammonemia when transplanted into mice with mild/severe OTC deficiency. Isotope-labeled ammonia-loading tests in post-transplant recipients confirm the graft’s efficiency in in vivo urea conversion. Moreover, organoid transplantation improves activity and survival rates in severe OTC-deficient mice. Overall, we demonstrate the therapeutic effects of clinically applicable hiPSC-derived organoids, which highlights their potential application in regenerative therapy.2026/04/01GSE263559GSM8194477GSM8194483GSM8194481GSM8194482GSM8194480GSM8194478GSM81944791707713497263559Homo sapiens