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First pig-monkey chimera engineered and born.

In the past chimeras, an unnatural amalgamation of two different species was the stuff of futuristic sci-fiction comics, today this promising genetic engineering technique is less scary as it becomes reality to offer solutions in a life-threatening worldwide donor organ shortage.

Xenotransplantation is the transplantation of living cells, tissues, or organs between different species, as opposed to allotransplantation between different individuals from the same species. It is hoped human organs can one day be grown on request in animal hosts, however, to enable this process transgenic animals must be genetically engineered, where the genetic material of a human and animal species are grafted together to produce a chimera.

The initial clinical attempts, however, faced technical and ethical issues prompting the research community to go back to preclinical studies which so far have shown a lack of progress in pig‐to‐nonhuman‐primate transplant models.

Non-human chimeras born alive

Now, a study from researchers at the University of Chinese Academy of Sciences engineers two pig-nonhuman-primate chimeras brought to full term and born alive, surviving for a few days after birth. The team states two piglets looked normal with a small proportion of their cells derived from cynomolgus monkeys. The opensource study is published in the journal Protein & Cell.

Previous studies show human pluripotent stem cell injections are believed to be the most promising method to generate chimeric organs for xenotransplantation. Unfortunately, ethical issues prevent the study of human chimeras in the late embryonic stage of development.

Primate embryonic stem cells, which have similar pluripotency to human embryonic stem cells, are a good model for studying interspecies chimerism and organ generation. It is unclear, however, whether primate embryonic stem cells can be used in chimeric genetic engineering. The current engineers pig-primate chimeras by injecting primate embryonic stem cells into fertilized pig embryos and then implanting them into surrogate sows.

The current study grew cells from cynomolgus monkeys in lab dishes, the cells were imbued with fluorescent proteins and derived to produce fluorescing embryonic cells. These glowing embryonic cells were then injected into prepared pig embryos which allowed the researchers to track the monkey cells as the embryos grew into piglets.

Results show the surrogates bore 10 piglets, of which two grew both pig and monkey cells, with between one in 1,000 and one in 10,000 functional monkey cells to pig cells. Data findings show fluorescent monkey cells are scattered throughout the chimera piglet’s organs, including the heart, liver, spleen, lungs, and skin. 

Growing entire organs in chimeras

The lab notes the piglets died shortly after being born, with the exact reason for their death unclear, however, they suspect the deaths are linked to the in vitro fertilization procedure rather than the injection of monkey DNA. They now aim to increase the proportion of monkey cells to pig cells in future chimeras, and eventually, grow entire monkey organs in their pigs.

The team surmises they have engineered two pig-monkey chimeras which went full term and were successfully delivered in a live birth. For the future, the researchers state they aim to grow human organs in animals for use in transplant procedures after a slew of ethical issues has been dealt with.

Source: The New Scientist

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