Researchers at the Xenotransplantation Research Center (XRC) are planning to transplant a pig’s cornea into a person this December.
If successful, it will mark the world’s first pig-to-human cornea xenotransplantation completed in step with guidelines by the International Xenotransplantation Association (IXA).
|Miniature pigs become preferred animal for xenotransplantation due to their physiological and anatomical characteristics.|
“We are the only institution in Korea to fulfill IXA guidelines, and we published the paper in 2015 in the American Journal of Transplantation,” said XRC Director Park Chung-Gyu, who is also a professor at the Department of Microbiology and Immunology, Seoul National University College of Medicine.
To get a clinical trial, the IXA requires the organization to finish eight pig-to-monkey xenotransplantations consecutively. Five out of the eight monkeys should have normal cornea function such as standard cornea thickness and clarity for more than six months, and one monkey should maintain that for more than a year.
Park stressed that Seoul National University College of Medicine’s XRC had become a global institution by fulfilling IXA guidelines and having designated pathogen-free pigs, a strong islet isolation team, and a nonhuman primate center that monitors animals just like human patients.
In an interview with Korea Biomedical Review, Park, who also serves a council member of the IXA and the president of the Korean Society of Immunologists, outlined how xenotransplantation research has been unfolding at a rapid pace around the world and in Korea, despite deficiencies in the Korean regulatory environment.
New hope for organ failure patients
Xenotransplantation, which refers to organ and tissue transplants done between different species, is emerging as a new hope for patients who need organ transplantations but don’t have an organ donor.
Patients facing organ failure have only a handful of treatment options with transplantations often being the only viable choice for survival. Despite the urgency, many patients have been put on waiting lists because of a lack of organs. Data shows around 6,000 people in the U.S. die a year while waiting.
|XRC researchers transplant a pig’s islet into a monkey.|
Organ shortages have been a problem around the world but especially in Korea where the number of organ donations remains strikingly low. According to an annual report by Korea Network for Organ Sharing (KONOS), around 4,100 organ transplants were completed in Korea in 2015 while about 27,500 people remained on the waiting list, indicating only about 15 percent of people who needed them got them. The problem has also indirectly fueled illegal organ harvesting in China
Pigs as rising stars
As a possible solution to organ shortage, scientists around the world have been working to develop xenotransplantation techniques and methodology, especially those concerning pig-to-man organ transplantations.
Pigs have proved useful – even more than monkeys, chimpanzees, and baboons – because of their anatomy and physiological makeup. Miniature pigs, which weigh around 80 kilograms and at most 120 kilograms, are preferred because they can be bred in specific conditions and produce up to eight litters per delivery. Monkeys, while more similar to humans evolution-wise, are an endangered species and only give birth to one offspring, making them a less favorable candidate for xenotransplantations.
Pigs also pose less risk for serious trans-species infection. Concerns about a retrovirus called Porcine Endogenous Retroviruses (PERV) spreading and causing an epidemic among humans have been quelled mainly due to research that showed the infection not to affect humans unless in abnormal conditions. Researchers have also used CRISPR-Cas9 gene editing technique to produce PERV-free, living pigs, the Independent reported.
Pig genes can also be manipulated to reduce immune reactions that lead to organ rejection upon transplantations. Humans have natural antibodies against a pig’s galactose-alpha-1,3-galactose, called the alpha-Gal. Human antibodies attack the alpha-Gal, leading to what’s called a hyperacute rejection. To deal with hyperacute rejection, a group of scientists in 2003 created a pig without the alpha-al, which “marked an epoch” and propelled xenotransplantation research forward, Park said.
XRC pushes for research despite lack of regulation
|Professor Park Chung-kyu, director of the Xenotransplantation Research Center, says the sector’s future is bright – provided the government comes up with adequate regulatory supports.|
XRC, Korea’s leading xenotransplantation institution, is now preparing to complete pig-to-man cornea xenotransplantation within this year. Despite their achievements, Park pointed out that Korea lacks the necessary regulations that help scientists focus on their research safely.
In the Changsha Communique, the World Health Organization outlines that xenotransplantation clinical trials and procedures need to be regulated efficiently and “xenotransplantation [should not be done] in the absence of effective regulation by the government.”
However, conducting xenotransplantation without government regulation is precisely what the XRC has been forced to do, Park said. The XRC head pointed out the Korean government had poured significant sums of money into xenotransplantation research for the past decade but failed to create the necessary regulations – leaving scientists in a figurative black hole where the only option they have is to succeed.
“In the absence of regulations, as is the case for xenotransplantations, if something goes wrong, the doctors will take the blame. Right now, Korean doctors take all of the responsibility,” Park said.
“If we are successful with the xenotransplantation in December, we won’t have a problem. But if we fail, we will take all the blame because we did it without any regulations,” Park said.
The lack of interest and proper communication from the MFDS and the Ministry of Health and Welfare (MoHW) has left scientists no choice but to go forward without any overarching regulations on issues such as microbiological safety, PERV, and long-term patient monitoring, he said.
“We have communicated with the MoHW and MFDS for a long time on the issues of regulation, but they have made no practical advancements. Nor have they tackled it actively,” Park said. XRC is applying for approval from the Institutional Review Board (IRB) for pig-to-man islet xenotransplantation by the end of this year, he added.
“After getting the approval from the IRB, we hope to get a review from the Bioethics Committee of International Xenotransplantation Association for ethical and social xenotransplantation issues and the National Bioethics Committee on national issues depending on the availability. We hope MoHW or MFDS will handle the issue,” Park added.
“Our program will end in May 2019. This is a huge program the government invested in for more than 10 years. Regulations should exist, and we’d like to get it within our research period,” he said.
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