Longevity Briefs: Another Step Towards Growing Human Organs From Scratch

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Millions of people suffer from organ failure and need a donor organ to survive. The majority of those people need kidney transplants. Unfortunately, the demand for organs far exceeds the supply and even when a donor can be found, there are risks of immune rejection.

One approach to solving this shortage is the use of ‘humanised’ animal organs. Using gene editing, molecules that would result in rejection of an animal-derived organ are removed, allowing them to be transplanted into humans. Some progress has been made towards this in recent years, such as the first ever pig to human heart transplant last year (though sadly the recipient did later die), as well as a study last month showing the first example of normal kidney function in pig to human transplantation. 

Though this progress is welcome, an organ from an animal is unlikely to function as well as a human organ. That’s why scientists have been exploring ways to create human organs in animals, such as pigs, using stem cells. Stem cells are special cells that can turn into any type of cell in the body. By introducing human stem cells into animal embryos, scientists hope to generate organs that are compatible with humans and can be used for transplantation.

What did the researchers do: In this study, researchers from China generated human induced pluripotent stem cells (iPSCs). These are stem cells that are derived from adult human cells, such as skin or blood cells.

The researchers then took pig embryos and used CRISPR/Cas9 gene editing to delete two genes that are essential for kidney development in pig embryos. The human iPSCs (which had also undergone gene editing to make them more resistant to cell death and more compatible with the pig environment), were then injected into the pig embryos, and those embryos were transferred into 13 surrogate sows.

After 28 days, researchers successfully harvested five embryos and examined the developing kidneys.

Key takeaway(s) from this research:

• Embryos developed kidneys containing up to 60% human cells, the highest percentage yet observed.
• The kidneys appeared to develop normally, generating kidney tubules and filtering blood.
• The success rate was low and the presence of pig cells would still cause problems for human transplantation.

Researchers found that the developing kidneys contained 50-60 percent human  cells, which is the highest percentage of human cells ever observed in any organ grown inside a pig. It’s possible that this percentage would have increased with further development.

The kidneys also showed signs of normal development and function, such as forming tubules and filtering blood, suggesting that it is possible to generate a humanised organ inside an animal using stem cells and gene editing. 

This is a big step forward, but there are still some significant hurdles to overcome. About 1800 embryos were generated and transplanted, making the success rate very low. It’s not known whether the kidneys would have become fully mature and functional if development had continued. Furthermore, when it comes to organ rejection, being ‘mostly human’ isn’t good enough – it’s likely that even a small percentage of pig cells would cause problems when the kidneys were transplanted into humans.

The study also raised a few ethical concerns, as some human iPSCs developed into neurons within the central nervous systems of the embryos. This process was random and not likely to result in pigs with human brains. Even so, this should be easy to overcome with more gene editing. Researchers are optimistic that with more fine-tuning, viable organs for human transplantation could be generated. Using the organ recipient’s own cells could also eliminate the risk of immune rejection.