preprints.org > medicine and pharmacology > transplantation > doi: 10.20944/preprints202304.0111.v2

Preprint Communication Version 2 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 6 April 2023 / Approved: 7 April 2023 / Online: 7 April 2023 (04:10:53 CEST)
Version 2 : Received: 8 April 2023 / Approved: 10 April 2023 / Online: 10 April 2023 (09:14:25 CEST)

Recently, two pig-to-human kidney transplants and a pig-to-human heart transplant were completed. The kidney trials involved a patient who was deceased and a patient who was brain dead. They seemed to indicate that pig kidneys can be at least somewhat functional in humans. However, patients still have to be under severe immunosuppression - and the first patient to receive a porcine heart passed away after two months. It is difficult to know exactly which proteins we need to overexpress or underexpress/knockout in a porcine organ to negate the human recipient’s immunological response to it. And testing different porcine organ genetic modifications in baboons can cost around $500,000 per transplant. But there might be a way to decrease immunogenicity where we don’t have to worry so much about modifying the animal’s organs genetically. First, however, we would have to prevent complement factor-mediated lysis of the porcine vascular endothelial cells, which we have made much progress on with triple knockout animals. Then, we could modify the porcine organ so that the cells of said organ secrete a small molecule or peptide that acts as a chemorepellent for the host immune cells. The host immune cells can be modified via bone marrow transplant or vector delivery to express the chemorepulsion receptor.

Xenotransplantation; chemorepulsion; adaptive immunity; innate immunity; dysregulated coagulation; complement cascade

Medicine and Pharmacology, Transplantation

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