Human-Pig Chimeras To Solve Organ Donor Shortage

The story of the Minotaur, with the head of a bull and the body of a man, slayed by Prince Theseus in the heart of a maze, is an old one. However, scientists’ recent attempts to create human chimeras (organisms made of cells from two genetically different types of cells) as organ donors are anything but a myth.

Photo credit: University of Liverpool Faculty of Health and Life Sciences
Photo credit: University of Liverpool Faculty of Health and Life Sciences

With growing populations and ever-increasing life expectancies, demand for replacement organs far outweighs supply. In fact, more than 350 people die each year in the UK waiting for a donor organ. With a cheap and unlimited source of suitable organs, quality of life for desperately ill patients currently waiting years for transplants would be massively increased. Using innovative stem cell technology, growing organs in pigs and other animals is set to blur the boundary between humans and animals.

Xenotransplantation – transplanting animal cells or organs into humans – is nothing new. Many diabetics have been successfully treated with pig pancreatic cells, and heart valve replacements are more frequently being obtained from pigs. These procedures, which use only a few cells, have acceptably low rejection rates, unlike failed attempts at full-organ transplants.

However, scientists at University of California, Davis, lead by Professor Pablo Ross, are now attempting to transplant not animal cells themselves, but rather grow human organs inside pigs. Human pluripotent stem cells, when injected into animal embryos, can differentiate into all specialised cell types needed to make a heart, kidney or pancreas. As the human cells grow with the pig cells, the embryo’s immune system learns to not reject them.

Genetically modifying pigs so human organs grow exclusively should avoid previous issues of the pig cells outcompeting their human counterparts. For example, genes needed to develop a pancreas are excised from pig stem cells using Crispr gene-editing technique. Injected human stem cells then divide and differentiate to populate the space, growing into a human pancreas. Currently only allowed to mature for 28 days, the embryos are expected to mature like any other pig, except that they are carrying a human organ.

Unsurprisingly, this research is very controversial. Firstly, at an estimated cost of $100,000 to $500,000 per organ, this is currently not a financially realistic treatment option. Secondly, the National Institutes of Health (NIH) suspended all funding on research in this field in 2015 to allow more time “to evaluate the state of the science in this area, the ethical issues that should be considered, and the relevant animal welfare concerns”.

Animal welfare concerns could arguably not be considered a priority in hindering essential research, given that as a society, we slaughter millions of animals each year for meat. The ethical issues are more justifiable given the uniqueness of the project. Will the human stem cells differentiate into all cell types, not just the desired organ? For example, could human brain cells develop in the pig to grow human brains inside a pig’s body?

If these concerns can be overcome then the next generation of transplantation could be one step closer. Professor George Church, from Harvard Medical School, believes chimeras could be “superior to human donors” as the organs are “very clean, available on demand and healthy”. Looking further into the future, it is anticipated this treatment will provide the “elixir of life” for us all; replacing ageing hearts, lungs and kidneys with those a quarter of our age.

 

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