A team of researchers in China have genetically engineered a pig with human DNA and transplanted skin grafts onto monkeys in a “milestone” they say will pave the way for future skin and organ transplantations.
In the United States alone, more than 113,000 people are awaiting organ transplants yet just over 36,000 occur each year, according to the Health Resources and Services Administration. Xenotransplantation, the process of grafting or transplanting organs or tissues between different species, may be a solution to the shortage of organs around the world and provide treatment for patients with terminal organ failure, write the researchers in bioRxiv, a pre-print server for biology that has not been certified by peer-review for publication in a journal.
Pigs are widely used in biomedical research yet they are not phylogenetically close to humans, so rejection and incompatibility can occur. Genetically modifying donor pigs to serve as a potential organ source may provide a potentially viable solution, but the necessary combinations of genetic modifications in pigs for human xenotransplantation have not yet been determined.
To test these parameters, researchers at the First Affiliated Hospital of Nanchang University in China removed key pig genes that trigger organ rejection and added eight human genes to modified pigs in order to further reduce the chance of an organ being rejected. Skin was then transplanted from the pigs to monkeys and survived up to 25 days without the monkeys requiring immunosuppressive drugs.
“Genetic modification of the pig is necessary to account for the differences between the pig and human genome, especially from the immune and molecular compatibility aspects,” write the authors, adding that CRISPR/Cas9 technology has accelerated this process but determining which combinations “remains an open question.”
The authors note that extensive genome editing in certain pig cells is not a practical endeavor because of the telomere length, which requires complex and extensive editing and a long cell culture time that may lead to cell aging or death. There is also a low risk that porcine endogenous retrovirus (PERV), a virus integrated into the genomes of pigs, could infect human hosts. Even so, the findings have “great potential for clinical value to save severe and large area burn patients and other human organ failure.”
“As the skin is considered the vital, unique and immunogenicity organ, our preliminary success in skin xenotransplantation using the combination of multi-gene modified pig in NHP provides the approval of the concept, paves a way to initiate the other organ preclinical trial and clinical trial, implies a success of these organs’ xenotransplantation,” writes study author Wang Gang in a comment, adding that genetically altered pigs may have the “potential to become an unlimited organ source for future clinical transplantation.”
The researchers add that their findings may also have applications for human disease modeling and potentially help to one day establish disease-resistant animals.