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Genetically engineered pig hearts transplanted in two brain-dead patients reveal more about immune response

by rajeshdevjee@gmail.com
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Study design and sampling timeline. Credit: Nature Medicine (2024). DOI: 10.1038/s41591-024-02972-1

A large team of biomedical researchers affiliated with a host of institutions across the U.S., the U.K., Saudi Arabia and France, has learned more about many of the factors involved in xenotransplantation as they conducted a large number of tests on two brain-dead human patients that had received genetically engineered pig hearts.

The group has published a paper in the journal Nature Medicine, outlining their findings.

As the shortage of organs available for people who need continues, are exploring the possibility of using genetically engineered organs from animals instead. As part of that effort, research has been conducted into the factors involved that may or may not allow such patients to accept xenotransplanted organs and continue living.

Thus far, efforts to use animal organs in humans have been only partially successful—patients live for just a few months afterward. In this new study, the researchers sought to learn more about what happens to the human body when it receives an organ transplant from another animal—both positive and negative.

To that end, they gained permission from the families of two people who were brain dead to allow them to transplant genetically engineered pig hearts and then to conduct a huge number of tests of samples collected over a three-day period.

The transplants were done back in 2022 at the NYU Langone Health Center for Biospecimen Research and Development—the patients were kept alive via ventilators. The two pig hearts had both been genetically modified to give them human transgenes and to take out genes encoding for antigens. Blood samples were collected from both patients every six hours, before, during and after transplantation. Tissue samples were also collected periodically.

Included among the tests on the samples were RNA sequencing, , cytokine profiling, and lipidomics—the aim was to better understand immune and other responses to the sudden appearance of a foreign organ in the body.

The research team could see evidence of gene expression shifts in one of the patients and an uptick in T cell and killer immune cell activity—that outcome was described as poor, likely due to receiving an undersized heart. The team expects to learn more as further study of data from the transplants is carried out.

More information:
Eloi Schmauch et al, Integrative multi-omics profiling in human decedents receiving pig heart xenografts, Nature Medicine (2024). DOI: 10.1038/s41591-024-02972-1

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Genetically engineered pig hearts transplanted in two brain-dead patients reveal more about immune response (2024, May 20)
retrieved 20 May 2024
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