Pig Heart Kept Beating in Baboon for Years

One day, cardiac patients may enjoy a new lease on life with pig hearts beating in their chests, said researchers reporting a major advance Tuesday in cross-species organ transplantation.

Given the dire shortage of organ donors, the use of animal hearts, lungs or livers to save human lives has long been a holy grail of medical science.

But organ rejection has stood stubbornly in the way.

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On Tuesday, scientists from the United States and Germany said they had succeeded in keeping transplanted pig hearts alive in baboons, primate cousins of humans, for a record 2.5 years.

Their method uses a combination of gene modification and targeted immune-suppressing drugs.

"It is very significant because it brings us one step closer to using these organs in humans," said study co-author Muhammad Mohiuddin of the National Heart, Lung and Blood Institute in Maryland.

"Xenotransplants - organ transplants between different species - could potentially save thousands of lives each year that are lost due to a shortage of human organs for transplantation," he told AFP by email.

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In experiments with five baboons, the hearts survived for up to 945 days, breaking previous records held by the same group of researchers.

The hearts did not replace those of the monkeys, but were connected to the circulatory system via two large blood vessels in the baboon abdomen.

The transplanted heart beat like a normal heart, but the baboon's own heart continued the function of pumping blood - a known method in studying organ rejection.

Donor organs are often rejected by a recipient's immune system, which can recognise it as foreign, and thus a threat.

In this trial, the donor organs came from pigs which had been genetically modified to have high tolerance to immune response, basically making them invisible to the recipient's natural defence system.

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The scientists also added a human genetic signature to the pigs that help prevent blood clotting.

The recipient baboons were given a drug that suppresses immune response.

Scientists have been experiment with the transplantation of primate kidneys, hearts and livers into humans since the 1960s. None survived beyond a few months.

Given their genetic proximity to humans, primates were initially thought to be the best donor candidates. But there is no large source of captive-bred apes - which take long to grow and mature, and some like chimpanzees are endangered.

Their genetic closeness also poses a higher danger of inter-species disease transmission, as well as ethical questions.

Pigs have since emerged as better donors. Their hearts are anatomically similar to ours, they pose less of a disease transmission risk, they grow up fast and are already widely farmed.

In these xenotransplant trials, baboons serve as human models.

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The next big test will be full pig-to-baboon heart transplants, said Mohiuddin, adding that porcine hearts could make their way into human chests "in the foreseeable future".

"In our opinion, this regimen appears potentially safe for human application for patients suffering from end-stage organ failure who might be candidates for initial trials of xenotransplantation," wrote the study authors.

The work was published in the journal Nature Communications.

Chimeras

In Greek mythology, chimeras were vicious monsters feared by many. This fire-breathing animal had the head and body of a lioness, with a goat head protruding from her back and the tail of a snake. Today, “chimera” refers to an animal that has two or more different sets of genetically distinct cells working together. Remember the mouse with the ear on its back? The movie "Splice" showcases a chimera experiment gone horribly wrong: scientists create a human-animal hybrid that becomes evil and goes completely out of control. While the movie is obviously science fiction, chimera experiments with human cells are not, and real life scientists have been conducting them for decades. We take a look at a few that have been successful in the past and how they’re advancing medicine.

Rabbit Eggs with Human Cells

The first successful human-animal chimeras were reported in 2003. Chinese researchers at the Shanghai Second Medical University successfully fused human cells with rabbit eggs. They were allowed to develop the eggs for several days in a petri dish before the embryos were harvested for their stem cells. Their hope was that this process could one day be used to grow cells or tissues for transplantation.

Pigs with Human Blood

A year after the successful Chinese chimera experiment, researchers at the Mayo Clinic in Minnesota announced they had created pigs with human blood pumping through their veins. What was startling about the animal is not only did the pig blood cells flow with human cells, but some of the cells merged together, creating pig-human cell hybrids. Scientists said this experiment can give them a better understanding of how viral infections can pass from animals to humans such as HIV and various others.

Sheep with Human Livers

One of the efforts behind creating chimeras is to generate animal specimens that could grow human organs to be farmed for transplantation. In 2007, scientists at the University of Nevada-Reno announced they could grow livers made up of 20 percent human cells in sheep. Dr. Esmail Zanjani injected either human adult stem cells derived from bone marrow, or human embryonic stem cells, into growing sheep fetuses. Zanjani said he uses sheep because the circulation systems of sheep and humans are similar.

Mouse-Human Liver

How do you develop treatments for liver infections and diseases only humans can get? Salk Institute researchers came up with one solution in February 2010. Using a mouse that was having liver problems of its own, the researchers replaced its liver with one that was made up of 95 percent human cells to study treatments for Hepatitis. Shown here is a cluster of mouse liver cells that have been replaced with human cells (shown in green). Typically, small animals can't be infected with Hepatitis, only humans and chimps can, but this "humanized" mouse not only became infected, it successfully responded to drug treatments. Scientists believe this experiment could open doors to finding cures for other human liver infections such as malaria.

Cow Eggs with Human Cells

British researchers were given approval to conduct human-animal hybrid research in 2008, a decision that researchers touted would give them the ability to possibly find a cure for Parkinson’s disease. Before, only human cells were allowed to be injected into human eggs, but the researchers argued that animal eggs are much more available. After given permission, researchers went to work using cow eggs. The nucleus of the cow egg -- the source of most DNA and shown here in blue -- was removed, and replaced with the nucleus of a human cell such as a skin cell. Once the egg was allowed to develop and multiply it would become a early-stage cloned embryo called a blastocyst. Scientists could then extract the stem cells from this blastocyst to use in disease treatments.

Cat-Human Hybrid Proteins

Allergic to cats? Then you’ll appreciate this experiment. The feline Fel d 1 protein found in cat saliva contains an allergen that affects humans. When cats lick themselves, the saliva on their fur dries and turns into dust. In April 2005, scientists at the University of California created a human-cat hybrid when they fused the Fel d 1 protein with a human protein known to suppress allergic reactions. The feline protein would bind to immune cells that would cause the reaction and the human protein would tell the immune cells to calm down. When tested in mice, the chimeric protein stifled the allergy, and researchers hope they can be used in the future to treat allergy sufferers.

Mouse-Human Brain

Irving Weissman, Stanford University professor and cofounder of the biotech company StemCells Inc., was granted permission by Stanford to create a mouse-human hybrid in 2005. Weissman and his team transplanted human-brain stem cells into the brains of mice with the intention to study neurodegenerative diseases such as Parkinson's and Alzheimer's. In his initial experiment, the human cells only made up less than 1 percent of the mouse brain. Shown here is an isolated mouse brain cell. In 2010, Stanford researchers announced they transformed mouse skin cells into fully functional neurons in a laboratory dish for the first time. They also announced in May that they successfully used mouse stem cells to develop sensory hair cells, which could combat human hearing loss.

Humanzee

We share over 98 percent of our DNA with chimpanzees, so would it be possible to create a human-chimp hybrid: a "humanzee," also called a "chuman" or "chumanzee"? In the 1920s, a Soviet biologist Ilia Ivanov artificially inseminated female chimps with human sperm, but the pregnancies didn't take. A chimp named Oliver became famous in the 1970s after it was thought he could be a human-chimp hybrid, because he walked upright. However, genetic testing in the 90s proved he was a chimp. Several researchers and citizens see such experiments has highly immoral and there is no known evidence of a human-chimp hybrid.