Tag: pigs

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World’s First Pig-to-Human Liver Xenotransplant in a Living Recipient

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Research in the Journal of Hepatology demonstrates that genetically engineered porcine livers can support key hepatic functions in humans

A landmark study in the Journal of Hepatology reports the world’s first auxiliary liver xenotransplant from a genetically engineered pig to a living human recipient. (Credit: Journal of Hepatology / Zhang et al.)

An important new study in the Journal of Hepatology, published by Elsevier, reports the world’s first auxiliary liver xenotransplant from a genetically engineered pig to a living human recipient. The patient survived for 171 days, offering proof-of-concept that genetically modified porcine livers can support key metabolic and synthetic functions in humans, while also underscoring the complications that currently limit long-term outcomes.

According to the World Health Organization, thousands of patients die every year while waiting for organ transplants due to the limited supply of human organs. In China alone, hundreds of thousands experience liver failure annually, yet only around 6000 people received a liver transplant in 2022. This pioneering case offers a potential new avenue to bridge the gap between organ demand and availability.

The case involved a 71-year-old man with hepatitis B-related cirrhosis and hepatocellular carcinoma who was not eligible for resection or human liver transplantation. Surgeons implanted an auxiliary graft from a genetically modified Diannan miniature pig with 10 gene edits, including xenoantigen knockouts and human transgenes to enhance immune and coagulation compatibility.

For the first month after surgery, the graft functioned effectively, producing bile and synthesising coagulation factors, with no evidence of hyperacute or acute rejection. However, on day 38, the graft was removed following the development of xenotransplantation-associated thrombotic microangiopathy (xTMA), a serious complication related to complement activation and endothelial injury. Treatment with the complement inhibitor eculizumab and plasma exchange successfully resolved the xTMA. Despite this, the patient later experienced repeated episodes of upper gastrointestinal haemorrhage and passed away on day 171.

“This case proves that a genetically engineered pig liver can function in a human for an extended period,” explained lead investigator Beicheng Sun, MD, PhD, Department of Hepatobiliary Surgery, and President of the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. “It is a pivotal step forward, demonstrating both the promise and the remaining hurdles, particularly regarding coagulation dysregulation and immune complications, that must be overcome.”

“This report is a landmark in hepatology,” commented Heiner Wedemeyer, MD, Co-Editor, Journal of Hepatology, and Department. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany, in an accompanying editorial. “It shows that a genetically modified porcine liver can engraft and deliver key hepatic functions in a human recipient. At the same time, it highlights the biological and ethical challenges that remain before such approaches can be translated into wider clinical use. Xenotransplantation may open completely new paths for patients with acute liver failure, acute-on-chronic liver failure, and hepatocellular carcinoma. A new era of transplant hepatology has started.”

“The publication of this case reaffirms the Journal of Hepatology as the world’s leading liver journal. We are committed to presenting cutting-edge translational discoveries that redefine what is possible in hepatology,” added Vlad Ratziu, MD, PhD, Editor in Chief, Journal of Hepatology, and Institute for Cardiometabolism and Nutrition, Sorbonne Université and Hospital Pitié Salpêtrière, Paris, France.

Source: European Association for the Study of the Liver

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A Synthetic Alternative to Pig-derived Heparin

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Photo by Corinna Widmer from Pexels

Scientists have developed a process to synthesise the vital blood thinner heparin, which is normally harvested from pig intestines. This synthetic heparin would help the quality control issues and shortages associated with pig-derived heparin.

The most expensive part of a pig is not a cut of bacon or a chop, but the part of the intestine used to make heparin. About 2000 pigs required to produce a kilogram of heparin, which provides medication to up to 6000 patients. In total, it is estimated that about one billion primarily Chinese food pigs each year also supply intestines for the extraction and processing of heparin.

However, this can cause problems for patients. When making medicines derived from animals, the chemical structure is rarely uniform. There are relatively common but harmless side effects, and in very rare cases severe and life-threatening immune reactions. Additionally, there are ethical and religious concerns for many patients. Bovine- and sheep-derived heparin are also produced but have the same concerns of being of animal origin. In fact, prior to 2000, heparin was derived from cows until the outbreak of mad cow disease.

Therefore, it has long been an ambition among researchers to make heparin in a laboratory to get cleaner heparin without side effects. Now researchers from the Copenhagen Center for Glycomics at the University of Copenhagen are ready with a study that shows that it is possible to make heparin without the use of animals.  which was published in Science Advances.

“By making heparin without the animal, you get a much cleaner and more uniform chemical structure. We show that we can do it in the laboratory, i.e. in a so-called ‘cell factory’, in the same way as many other types of medicine are made. It is a step in the direction of the development that has also happened with insulin, which was previously extracted from the pancreas in pigs before we learned to produce it in the laboratory,” explained Associate Professor Rebecca Miller, who led the study. 

There is already a synthetic alternative to heparin, but it is difficult to dose and can lead to overdose. Because of this, GPs often prescribe pig-derived heparin to their patients.

Heparin is today extracted from pig intestines’ mucosa. Due to the sheer number of patients who need the medicine, the scale of the production is vast, making quality control a recurring problem for manufacturers.

In 2008, a number of stocks of heparin from Chinese pigs were recalled when it was found that the medicine was contaminated. The case ended up costing the lives of more than 100 Americans.

“Of course you want to avoid that, in addition to moving the source from animals to laboratory cells. With our new technology, we have made a design for how to make heparin in a cell that is clean and uniform and it suggests that it has the same medicinal effect as market heparin. In this way, you potentially get a product that leads to neither common nor life-threatening side effects,” said Richard Karlsson, PhD, who has also contributed to the main author of the study.

Right now, the world is facing a shortage of heparin because swine flu has thinned the pig population in China, the largest heparin producer.
Next steps would be to scale up production to provide much larger quantities of the new synthetic heparin. 

Source: University of Copenhagen