A pig embryo at four weeks, which had been injected with human stem cells. Photo Credit:- (Salk Institute)

Now the world is one step closer to a human-pig hybrid, scientists at the Salk Institute for Biological Studies in La, Jolla, California announced on Thursday (26th January). For the first time, Stem cell scientists have successfully created human-pig chimera embryos that raises the prospect of being able to grow human organs inside animals for use in transplants. The creation of this so-called “chimera” (an organism that contains cells from two different species) named after the cross-species beast of Greek mythology, hailed as a significant first step towards generating transplantable organs like human hearts, livers and kidneys.

“The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that,” says lead investigator Juan Carlos Izpisua Belmonte, a professor in the Salk Institute of Biological Studies’ Gene Expression Laboratory. “This is an important first step.”

Though researchers have had great success producing rat-mouse chimeras (top), it has been more difficult to achieve chimerism with human and pig cells (bottom). (Wu et al./Cell 2017)

The experiment, described Thursday in the journal Cell, that human cells can be introduced into a non-human organism, survive, and even grow inside a host animal, in this case, pigs and pigs proved more challenging than anticipated. Adult human stem cells (known as intermediate induced pluripotent stem cells) were injected into the embryo of a young pig, then implanted the embryo in the uterus of a sow and allowed it to develop for 28 days/ four weeks, (the first trimester of a pig pregnancy) before being removed.

Injection of human induced pluripotent stem cells into a pig blastocyst. (Supplied: Juan Carlos Izpisua Belmonte / Cell Press)
Human stem cells being injected into a pig embryo. Pic Courtesy:- Salk Institute

After 28 days/four weeks of growth, the stem cells had developed into the precursors of various tissue types, including liver, heart and neurons, and a small fraction of the developing pig was made up of human cells. The pig-human hybrid is “highly inefficient,” meaning we’re not yet ready to take organs from the human-animal chimera and put them in human’s body, but it is the first step toward the development of animal embryos with functioning human organs.

The notion of creating human-animal chimeras has been controversial for several reasons and ethical questions, including worries that human cells could enhance the host animal’s intelligence or develop into eggs or sperm (the creation of animals with human qualities, and possibly intelligence). If too much human DNA is introduced in a pig’s embryo, it could result in a pig with a ‘human brain’. But last summer (August 2016), the U.S. government said it planned to lift the moratorium on the use of federal funding for such research in January.

Courtesy;-Salk Institute

Supporters of the research have also said that human-animal chimeras could lead to better ways of studying early human development and human diseases, as well as provided a realistic drug-testing platform for regenerative medicine. And ultimately for the generation of transplantable human organs to solve the worldwide shortage of organ donors.

Juan Carlos Izpisua Belmonte, who led the project, said that fears around chimeras were inspired largely by mythology rather than the realities of meticulously controlled experiments. But he acknowledged: “The idea of having an animal being born composing of human cells creates some feelings that need to be addressed.” “Not everything that science can do we should do. We are not living in a niche lab, we live with other people – and society needs to decide what can be done.”

Bruce Whitelaw, professor of animal biotechnology at the University of Edinburgh who was not involved in the study, described it as “exciting” because it “paves the way for significant advances.”

According to Darren Griffin, professor of genetics at the University of Kent, the “work will also help us better understand evolution, development and disease” and may eventually lead to a remedy for organ shortages.

In the new study, the researchers started by experimenting with rodents, to see if they could create mice that contained some rat cells. The researchers injected rat stem cells into mouse embryos and found that the embryos indeed developed into mice with rat cells present in organs throughout the body, forming the functional tissues of the organism’s heart, kidneys, lungs, eye, or pancreas. Overall, the rat cells made up a small portion of the cells in the various organs, typically less than 10 percent, while the mouse cells made up the rest.

The group tried making rat-pig chimeras, but this didn’t work (the species were too different). Then the researchers planned to introduce human stem cells into an organism. They decided to use cow and pig embryos as hosts (chosen because of these animals’ organs relatively similar size among the species than mice). Although their attempts to create a human-cow chimeric embryo were successful, experiments with pig embryos were easier and cheaper than cow, so the team zoomed in on pigs.

Photo Courtesy:- Cell

The research team from the Salk Institute of Biological Studies in San Diego said around 2000 human-pig chimeric embryos had been used in the research, and it involved 40 people including pig farmers, over a four-year period. They implanted the chimeras into surrogate mothers (41 surrogate sows), they let the chimera embryos grew between three and four weeks, to check whether and where the human cells were contributing. A month later, 186 embryos turned into chimeras (that were largely pig, with human elements in 1 out of 10,000 cells). However, many of the embryos were much smaller than normal and seemed to grow more slowly, the group reports Thursday in Cell.

Undated photo released by U.S. Salk Institute on Jan. 26, 2017 shows Jun Wu (front) and Juan Carlos Izpisua Belmonte, investigators of the U.S. Salk Institute for Biological Studies. In a bold but potentially controversial quest for solutions for the worldwide shortage of transplant organs, scientists attempting to grow human organs inside pigs have successfully grown the first chimera embryos containing cells from both humans and pigs, they said Thursday. photo Courtesy:- (Joe Belcovson)

According to the U.S. Department of Health and Human Services, about 120,000 people are waiting for organ donations right now. There are 6,500 people in the UK waiting for a transplant (including 150 children). Every 10 minutes, a sick person is added to the national waiting list for organ transplants and each day, 22 people on that list die for lack of an organ, according to statistics.

What if, rather than relying on a generous donor, you could grow a custom organ inside an animal instead?


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