Gene editing used to test novel preclinical model for pig to human kidney transplant
A study at the University of Alabama at Birmingham conducted the first successful clinical-grade transplant of gene edited pig kidneys into a human recipient using a novel human preclinical model.
A study from the University of Alabama at Birmingham (UAB; AL, USA) has reported the first successful clinical-grade transplant of pig kidneys into a human recipient in the American Journal of Transplantation. The study utilized a novel, human preclinical model to test the safety of the procedure by transplanting the kidneys into a brain-dead person.
Brain-dead organ donors have regularly been maintained on life support until the organs could be harvested but this is the first time transplantation has been tested on a human decedent. Extensive testing of humanized pig kidneys into non human primates has been unable to describe how the kidneys would tolerate a human environment because of biological differences between non human and human primates.
The kidneys originated from genetically modified pigs provided by Revivicor (VA, USA) a subsidiary of United Therapeutics Corporation (MD, USA). A total of ten genetic changes were made in the donor pig, with four knockout pig genes and six knock-in human genes.
The preclinical human model provides evidence about the viability of xenotransplantation, but the model is complicated due to the context of a brain-dead recipient. This is typically a hostile environment for the transplanted kidneys as it may delay recovery and limit the assessment of normal kidney function.
The UAB team did not observe signs of organ transplant rejection but there are slower types of rejection which take weeks or months to emerge.
Jayme Locke, transplant surgeon from UAB, stated that “trying to ascertain function in the face of brain death is always going to be challenging, ultimately, we will need to move into a Phase I clinical trial in which we transplant these kidneys into a living human being where the environment is more favorable for kidney recovery”.
Although there are over 800,000 Americans living with kidney failure, less than 25,000 kidney transplants are carried out each year. The preclinical human model could be the first step to solving this problem.
Sources:
(Epub ahead of print); https://www/eurekalert.org/news-releases/940647