Pigs with human immunity
Christopher Tuggle, Adeline Boettcher, The Conversation
We’re creating ‘humanized pigs’ in our ultraclean lab to study human illnesses and treatments
How Humanized Pigs will help to study and treat human diseases
Abbreviated translation: Timeweb company blog, Habr
The U.S. Food and Drug Administration (USFDA) requires that all new medicines be tested on animals before being sold to humans. Pigs are one of the best test subjects. They are even better than mice, because humans have much more in common with pigs. For example, size, physiological characteristics and genetic composition.
A team of researchers from Iowa State University has developed a way to make pigs even more "like" humans. They have already successfully transferred part of the components of the human immune system to pigs. This discovery can significantly accelerate research in various fields of medicine, including the development of vaccines against various types of viruses, cancer drugs and stem cell therapies.
Piglets with a human immune system. Ahlea Forster, CC BY-SA.
Existing biomedical models
Severe Combined Immunodeficiency (Severe Combined Immunodeficiency), abbreviated TKID, is a genetically determined condition in which there is a violation in the formation of the immune system. Severe combined immunodeficiency can manifest itself both in humans (this was ironically beaten in the films "Under the Hood" and "The Guy from the Bubble") and in animals, including mice.
In the 1980s, researchers found out that it was possible to plant human immune cells in mice to further study the disease. Such mice are called humanized, that is, "humanized". They have been used for the last 30 years to study a lot of aspects of human health.
Mice are more often used in biomedical research than other animals, but the results obtained on rodents cannot always be compared with those that doctors receive when studying people. All because of the difference in metabolism, size and function of cells.
Primates are also sometimes used as test subjects, and they are much better suited for these purposes, since they look more like humans. But it's unethical to experiment on monkeys. For this reason, in 2013, many research centers released most of the chimpanzees used in their work "into the wild" and now need alternative test subjects.
Pigs are a suitable option. They are similar to humans, and given the scale of piglets' use in the food industry, people do not have ethical dilemmas when considering pigs as material for medical research.
Humanized Pigs
In 2012, a group of researchers from Iowa and Kansas state universities was created. Among them are Jack Dekkers, an expert in animal genetics, and Raymond Rowland, a specialist in animal diseases. By a lucky chance, they were able to detect genetic mutations in pigs that cause severe combined immunodeficiency. After that, the group decided to try to make new biomedical models out of such pigs.
The Dekkers and Rowland teams have been working for almost ten years to adapt the TKID piglets to the needs of biomedical researchers. In 2018, they achieved some success when they worked together with physiologist Jason Ross in his laboratory. Together with Ross, they created pigs with even weaker immunity than those suffering from TKID, and successfully humanized them by planting human stem cells in the liver of growing piglets.
In the early stages of fetal development, implanted immune cells, being inside the liver, give the body the opportunity to produce new human cells. The researchers inject these cells into the piglet's liver using an ultrasound machine. While the fetus is developing, the transplanted stem cells begin to differentiate and turn into other types of cells, gradually spreading through the animal's body. As soon as TKID piglets are born, human cells can be found in their blood, liver, spleen and thyroid gland. And it is precisely because of this humanization that such pigs are so valuable for doctors.
Even now, people have managed to discover that human ovarian tumors are taking root in TKID subjects. This gives researchers the opportunity to study ovarian cancer in humans more deeply. According to the same principle, it is possible to study the treatment of burns, because human skin takes root on humanized piglets. And these are just a few examples.
A "bubble" for keeping TKID pigs in Ames, Iowa. Adeline Boettcher, CC BY-SA.
Pigs under the hood
Experimental animals are deprived of the most important components of their own immune system, so they are extremely vulnerable to various kinds of infections. They need to be kept in special sterile pens to reduce the pathogenic load.
TKID-piglets are raised in "bubbles" protected from microbes. High pressure is maintained in each pen, and water and air purification systems are installed at the entrances to prevent infections. Personnel working with test subjects are required to wear a special protective uniform. There are from 2 to 15 TKID individuals in one pen.
As with other animal studies, the question of ethics comes first. All medical protocols are approved by the Iowa State University's Institutional Animal Care and Use Committee and comply with the standards of The National Institutes of Health's Guide for the Care and Use of Laboratory Animals.
Pigs are checked twice a day by specialists who monitor their health. Veterinarians cooperate with the team of Dekkers and Ross. If one of the test subjects gets sick, and pills and antibiotics do not help, the animals are euthanized in the most humane way.
The task of specialists is to continue to adapt humanized animals to new experiments so that piglets are suitable for studying the effects of other diseases on immunity. The team hopes that in the future their TKID models will be the key to improving medical research and eventually help people.
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