A normal pig embryo (top row) and one with human kidney cells, labelled in red (below)
Wang, Xie, Li, Li, and Zhang et al./Cell Stem Cell
Kidneys that are more than 50 per cent human have started to grow in pigs for the first time after scientists created embryos made of human and pig cells and implanted them in sows for up to four weeks.
The research, conducted by Miguel Esteban at Guangzhou Institutes of Biomedicine and Health in China and his colleagues, brings us a step closer to being able to grow human kidneys in other animals to address the shortage of organ donors.
Over 100,000 people in the US alone are currently waiting for a kidney transplant, with 13 dying per day.
To get around the need for donors, it may be possible to grow human kidneys in other species like pigs that have similar organ sizes and physiology to us.
Esteban and his colleagues explored this idea by creating pig embryos that couldn’t form kidneys of their own, by disabling two key genes responsible for development of the organs.
Next, they introduced human stem cells into the pig embryos, hoping they would transform into kidney cells in the pigs and assemble into the relevant organs. The human cells were genetically engineered to help them integrate in the foreign environment by increasing the expression of two pro-survival genes.
The researchers implanted over 1800 of these hybrid human-pig embryos in the reproductive tracts of 13 sows. They only allowed the embryos to grow for 25 to 28 days before removing and analysing them because of ethical considerations, including the possibility of producing pigs with human-like brains if the human cells spread beyond the kidneys.
Only five of the embryos successfully implanted, but they were able to develop early kidney structures, including miniature tubules, that were made of 50 to 65 per cent human cells and the rest pig cells.
“This is a very important study,” says Jun Wu at the University of Texas Southwestern Medical Center. Wu and his team reported their creation of the first human-pig embryos in 2017, but were only able to incorporate a very small proportion of human cells, which didn’t assemble into organs.
Esteban and his colleagues tracked where the human cells went in their pig embryos by tagging them with a red fluorescent marker. They found that very few became incorporated in the early central nervous system or other organs, which Wu says is reassuring.
The researchers have now received approval from their institute’s ethics committee to let such human-pig embryos develop for up to 35 days to see if the humanised kidneys continue to mature properly and to ensure minimal human cells end up in other organs. “We will move forward step by step before reaching full term [of gestation],” says Esteban. They are also looking at growing other human organs like the heart and liver in pigs, he says.
Aside from this approach, other groups are working on ways to use pig-only organs for transplant into people. On 14 July, for example, surgeons at NYU Langone Health successfully transplanted a pig kidney into a brain-dead man. The kidney came from an animal that had a single gene knocked out so that its organs wouldn’t trigger an immune reaction in human recipients. A spokesperson for NYU Langone Health told New Scientist that the man’s kidney is still functioning properly almost two months later.
Wu believes that a combination of these two approaches – growing kidneys that are mostly human in pigs and also knocking out genes that might trigger immune reactions – may end up working best.
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