Japanese scientists have declared that replacement pancreas for a mouse was grown successfully in an animal of a different species.
Globally demand for organ transplants surpasses supply by a factor of thousands. Just in the US, nearly 100,000 people are on donor organ waiting lists.
Now researchers in Japan have opened the door for a solution by showing that it’s possible to grow a genetically compatible organ in an animal of a different species and then transplant it into a recipient to treat a disease. The research is described in a paper published in the journal Nature.
Diabetic mice were given replacement pancreas tissue grown in rats, reversing their diabetes for over a year. To achieve this, the scientists injected mouse stem cells into developing rat embryos. This produced embryos known as chimeras, in which the tissues were a mixture of mouse and rat cells.
The rat’s DNA had been genetically modified to deactivate a gene called Pdx-1. This is the main switch that controls the development of the pancreas, and so the removal of this gene prevents the rat cells from turning into pancreas cells.
But the injected mouse cells still have a working Pdx-1 gene, so the pancreas that forms in the rats is made up almost exclusively from mouse cells. Because the pancreas also contains blood vessels, and these still contain rat cells.
Yamaguchi and his team then isolated the insulin-producing “beta” cells from the pancreas tissue. They implanted them into mice with a form of diabetes caused by the loss of their pancreatic cells.
Other than administering a short five-day course of immunosuppression to their mice to guard against the immune rejection of any rat blood vessel cell in the transplants, the recipient mice received no other treatment. Nevertheless, their blood sugar levels returned to normal and remained well-controlled for over a year following the transplant.
This shows that “interspecies organogenesis” as the technique is known is theoretically and practically feasible. In the future, this can be translated to humans, but this will still take a long time.
The reason for Zhou’s note is that the current experiments were made simple by the knowledge of the Pdx-1 gene, which alone can deactivate the formation of the pancreas. Other organs will certainly not be so simple to manipulate.
“The eventual aim would be to grow human organs in pigs or sheep. But major technical challenges lie ahead, like the rejection of human organs(graft rejection) by the host animal’s immune system,” warns Zhou.