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Given the persistent scarcity of donor organs, there is growing anticipation that pig\u2010to\u2010human islet xenotransplantation will emerge as the definitive beta cell replacement therapy for this condition. The liver is the site of preclinical pig\u2010to\u2010NHP islet transplantation as well as allogeneic clinical transplantation, yet its pathology following islet transplantation remains poorly understood. Based on our observations of post\u2010transplantation periportal pathologic changes in primate models, we have conducted a retrospective study examining the hepatic pathology in pig\u2010to\u2010NHP islet recipients with short\u2010term graft survival, employing a state\u2010of\u2010the\u2010art spatial transcriptomic platform within the vicinity of the islet implantation site. Post\u2010transplantation liver tissue could be easily demarcated into three transcriptionally distinct regions, consistent with its histology. A notable elevation in adipogenesis and non\u2010alcoholic fatty liver disease (NAFLD) pathways was observed, exemplified by increased expression of <jats:italic>SREBF1<\/jats:italic>, <jats:italic>IGF1<\/jats:italic>, <jats:italic>CEBPA<\/jats:italic>, <jats:italic>FASN, GCK<\/jats:italic>, and <jats:italic>SCD<\/jats:italic>. We furthermore discovered that, despite the decreased severity of the multifocal white lesions indicated by gross examination at 33\u00a0days post\u2010transplantation, there was still evidence of fatty liver disease at the transcriptional level. These results warrant further research into the relationship between intrahepatic islet transplantation and the hepatic microenvironment.<\/jats:p>","DOI":"10.1111\/xen.70062","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T03:06:02Z","timestamp":1750734362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial Transcriptomic Analysis Reveals Increased Adipogenesis and Triggering of the Non\u2010Alcoholic Fatty Liver Disease Pathway in Pig\u2010to\u2010NHP Islet Recipients\u2019 livers During the Early Post\u2010xenotransplant Period"],"prefix":"10.1111","volume":"32","author":[{"given":"Yoon Ji","family":"Bang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul South 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