Changes in sperm engineering have reduced the chances of transplanted pig organs being rejected by human patients. A new technique suggests the success rate could be improved from four per cent to 88 per cent, according to the journal, Proceedings of the National Academy of Sciences. Until now researchers had relied on injecting a human gene into fertilized pig eggs to create animals whose organs could be harvested for use in humans.
The possibility of generating transgenic pigs efficiently and reproducibly will be an advantage for creating multi-transgene pig donor animals. But too often the animals fail to pick up the human gene and the organs have only been successful in four per cent of cases. But a team led by Mariluisia Lavitrano, at the University of Milano-Bicocca in Italy, have found that by modifying the DNA in pig sperm, rather than in the eggs, they can dramatically reduce chances of organs being rejected.
Of 93 piglets produced from the treated sperm, 57 per cent had the human gene in their organs. When unsuccessful fertilizations were excluded from the total of eight carried out, the success rate rose as high as 88 per cent. Furthermore the gene, called hDAF, was functional in multiple organs, including the heart, lungs and kidney.
Laboratory tests showed that pig cells with the human protein produced by the gene were resistant to attack by the human immune system. Lavitrano's team had previously demonstrated the technique, sperm-mediated gene transfer (SMGT), on mice. They wrote: “Pig is the most likely donor animal for xeno-transplantation of organs, but may well require multiple transgenes to be a satisfactory donor for humans. Given the high efficiency of transgenesis, SMGT could greatly facilitate the production of such pigs.”
Fresh pig sperm was incubated in a medium that contained the human DNA. The sperm naturally incorporated the human gene, which was then passed on to the offspring after fertilization.