Update: Just realized that the research article is quite outdated, published in September 2023, but the popular science article is new.
Bad news! However, I bet this issue will be overcome soon! Hopefully, sooner than later we will not have to rely on pigs anymore.
"... “Xenotransplantation could provide an unlimited and renewable source of organs,” ...
Over the past few years, the science of xenotransplantation has greatly advanced because scientists managed to prevent hyperacute organ rejection using genetically modified pigs. But ... recently found that humans still react to pig organs—these responses are just subtler and delayed. ..."
"... The study ... delved into the patients’ immune responses and revealed a unique form of rejection mediated by antibodies. Despite initial success, these findings underscore the need for a deeper understanding of the immune interactions between humans and pig organs in xenotransplantation.
The innovative approach employed advanced immunology and molecular microscopy technologies to precisely characterize immune cells within the transplanted organs. The results revealed a distinctive rejection pattern involving innate immune cells, a type of immunity shared across species, expressing genes typical of human organ rejection mediated by antibodies.
While this form of rejection poses challenges, it also provides valuable insights. Researchers can now identify molecular targets to optimize genetically modified pig models and develop immunosuppressive treatments. Existing treatments for antibody-mediated rejection in human transplantation may also be adapted for xenotransplantation. ..."
From the abstract:
"Summary
Background
Cross-species immunological incompatibilities have hampered pig-to-human xenotransplantation, but porcine genome engineering recently enabled the first successful experiments. However, little is known about the immune response after the transplantation of pig kidneys to human recipients. We aimed to precisely characterise the early immune responses to the xenotransplantation using a multimodal deep phenotyping approach.
Methods
We did a complete phenotyping of two pig kidney xenografts transplanted to decedent humans. We used a multimodal strategy combining morphological evaluation, immunophenotyping (IgM, IgG, C4d, CD68, CD15, NKp46, CD3, CD20, and von Willebrand factor), gene expression profiling, and whole-transcriptome digital spatial profiling and cell deconvolution. Xenografts before implantation, wild-type pig kidney autografts, as well as wild-type, non-transplanted pig kidneys with and without ischaemia-reperfusion were used as controls.
Findings
The data collected from xenografts suggested early signs of antibody-mediated rejection, characterised by microvascular inflammation with immune deposits, endothelial cell activation, and positive xenoreactive crossmatches. Capillary inflammation was mainly composed of intravascular CD68+ and CD15+ innate immune cells, as well as NKp46+ cells.
Both xenografts showed increased expression of genes biologically related to a humoral response, including monocyte and macrophage activation, natural killer cell burden, endothelial activation, complement activation, and T-cell development. Whole-transcriptome digital spatial profiling showed that antibody-mediated injury was mainly located in the glomeruli of the xenografts, with significant enrichment of transcripts associated with monocytes, macrophages, neutrophils, and natural killer cells. This phenotype was not observed in control pig kidney autografts or in ischaemia-reperfusion models.
Interpretation
Despite favourable short-term outcomes and absence of hyperacute injuries, our findings suggest that antibody-mediated rejection in pig-to-human kidney xenografts might be occurring. Our results suggest specific therapeutic targets towards the humoral arm of rejection to improve xenotransplantation results."
Immune response after pig-to-human xenotransplantation: a multimodal phenotyping study (original news release) "In a groundbreaking study ... has achieved a major breakthrough in the field of xenotransplantation."
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