Applying integrative multiomic profiling in two human decedents receiving pig heart xenografts reveals early immune cell responses indicative of perioperative cardiac xenograft dysfunction
Year: 2023
Type: article
Abstract: Background: Recent advances in xenotransplantation in living and decedent humans using pig heart xenografts have laid promising groundwork towards future emergency use and first-in-human trials. Major obstacles remain however, including a lack of knowledge of the genetic incompatibilities between pig donors and human recipients, which may lead to harmful immune responses against the xenograft and/or physiological dysfunction. In 2022, two gene-edited pig heart xenografts were transplanted into two brain-dead human decedents, primarily to evaluate onset of hyper-acute antibody mediated rejection and sustained xenograft function over 3-days. Methods: We performed multiomic profiling to assess the dynamic interactions between two pig heart-xenografts transplanted into two human decedents. We generated transcriptomic, lipidomic, proteomic and metabolomics datasets, across blood samples every 6 hours, as well as histological and transcriptomic tissue profiling, over the 3-day procedures to biological changes that correlate with immune-related outcomes and xenograft function.
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4391550393