Prospects and Controversies

28-day-old pig embryo with human kidney replica. (Photo: GIBH)

This is a historic image. A team of researchers in China has successfully created a human organ clone in another animal for the first time.

The experiment, conducted with cloned kidneys in pig embryos, represents a step toward the dream of using other mammals as a source of organs for transplants. However, these “hybrid” organs still pose difficult ethical questions.

Researchers at the Guangzhou Institute of Biomedical and Health Sciences reprogrammed adult human cells to regain the ability to form any organ or tissue in the body. The team introduced these human pluripotent cells into pig embryos that had been genetically modified so that they would not develop into pig kidneys. The human cells filled in the gap and created a “rudimentary” kidney, an intermediate stage of the renal system called the mesonephros.

The team transferred a total of 1,820 embryos into 13 sows, then terminated the pregnancies at 25 and 28 days (about a quarter of the normal gestation period for pigs) for evaluation. The results showed that five of the selected embryos had normal kidneys during development, with the ureters beginning to form to connect to the bladder. These kidneys contained 50 to 60 percent human cells.

The research was led by Chinese scientist Liangxue Lai, but the idea was initiated by a team led by Spanish researcher Juan Carlos Izpisua. In 2017, Izpisua announced the creation of human-pig embryos with a ratio of 1:100,000 human cells to pig cells. Those pioneering experiments were conducted at the University of Murcia (Spain) and at two Murcian farms, despite fierce debate by a committee of experts at the Carlos III Health Institute. The committee eventually gave the go-ahead for the trials despite the “biological risks inherent in the creation of pig-human chimeras,” but on the condition that none of the animals with human cells could reproduce.

A 28-day-old pig embryo grew a kidney that was half human cells. (Photo: GIBH)

Mr Izpisua welcomed the new research, which he was not involved in. “They go a step further and show that cells can be spatially organized and create organized tissue structures,” said the researcher, who is also director of the San Diego Institute of Science at Altos Laboratories in the US.

“It is not yet possible to grow adult human organs in pigs, but this research brings us one step closer. It is a big step forward,” said Izpisua.

According to official data, around 150,000 organs are transplanted worldwide each year, but in the US alone, there are 100,000 people on the waiting list for an organ transplant and 17 of them die every day.

Liangxue Lai and a team led by Spanish researcher Miguel Angel Esteban are now working toward the goal of producing mature kidneys, although they still have technical and ethical hurdles to overcome. One of the red lines is preventing human cells from escaping the kidney and integrating into the pig’s brain or gonads (testes or ovaries).

“The question is whether it is ethical to let pigs be born with adult cloned kidneys. It will all depend on the extent to which the human cells contribute to the pig’s other tissues,” said Esteban.

His research, published on September 7 in the journal Cell Stem Cell, showed that “very few” human cells were dispersed throughout the brain and spinal cord of pig embryos. “To eliminate any kind of ethical issues, we are further modifying the human cells so that they cannot enter the central nervous system of the pig in any way,” the Spanish doctor said.

In 2020, a team from the University of Minnesota successfully created human endothelium (the inner layer of blood vessels) in pig embryos.

A year later, the same team, led by Mary Garry and Daniel Garry, created 27-day-old pig embryos with cloned muscles.

Spanish doctor Miguel Ángel Esteban (right) and his Chinese colleague Liangxue Lai, at the Guangzhou Institute of Biomedicine and Health. (Photo: GIBH)

With the new experiment in China, nephrologist Rafael Matesanz, founder and former director of the National Transplant Organization in Spain, noted that this is the first time a human organ has been created inside another animal. “ Conceptually, this is a very important and meaningful step, but it is not a prelude to kidney production ,” the nephrologist said.

Matesanz was one of the members of the commission that authorized Izpisua's experiments in Murcia. In his opinion, it is “doubtful” that an experiment like the one being conducted in Guangzhou would be approved in Europe, because there is a possibility that some human cells could invade the brain of the pig embryo, which has indeed happened.

“ The main risk is that the cells will go to the central nervous system and create human-pig bodies. Or that they will go to the reproductive system ,” he warned.

The founder of the National Transplant Foundation believes that “a much more promising path” is to create genetically modified pigs so that pig organs do not cause rejection in humans after transplantation. On September 25, 2021, a team of surgeons at New York University successfully transplanted a pig kidney into a brain-dead woman. On January 7, 2022, after surgery at the University of Maryland Medical Center, American citizen David Bennett became the first person to have a beating pig heart in his chest. Bennett died two months later of heart failure, but there was no obvious sign of organ rejection, despite his heart being infected with a swine virus.

Spanish chemist Marc Güell is one of the founders of eGenesis, an American company that modifies pig DNA to create pig organs for human transplants. Mr. Güell also welcomed these new results: “ It may help to better understand where the current limits of chimerism between species are .”

Nephrologist Josep Maria Campistol, director general of the Hospital Clínic de Barcelona, emphasized all the prospects opened up by pig-human embryos. “ They could be an inexhaustible source of organs, and offer the possibility of creating specific, personalized human organs for certain patients, ” he said.

(Source: Tin Tuc Newspaper)

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