A team of Chinese scientists has successfully brought to term – for the first time – piglets injected with monkey stem cells, bringing researchers one step closer to being able to grow human organs inside animals.
The pig-monkey chimeras, an organism derived from two or more zygotes, or the eukaryotic cell formed during fertilization that contains essential DNA, were born at the State Laboratory of Stem Cells and Reproductive Biology in Beijing, China and appeared normal. The animals were born alive and survived for several days. However, despite his passing, they mark a milestone in the race to grow organs in the laboratory.
“This is the first full-term pig-monkey chimera experiment,” lead researcher Tang Hai told New Scientist magazine.
Controversial experiment
Although the pig-monkey hybrids died within the first week of being born, the researchers found that both had DNA from macaque monkeys in their heart, liver, spleen, lung and skin (specifically, crab-eating macaque – Macaca fascicularis -) But they were not found in other organs, such as the testes and ovaries, due to the low rate of hybridization, the researchers said.
They were reared from more than 4,000 five-day-old embryos that were implanted in the uterus of a sow using the in vitro fertilization (IVF) technique to achieve pregnancy. The team genetically engineered the monkey cells to produce a fluorescent protein that allowed the researchers to track the cells; these modified cells were injected into the pig embryos five days after fertilization.
Of all the embryos, only ten reached full term and managed to be born alive. Of these ten, only two of them had monkey cells, that is, “true” chimeras.
Of course, as we have seen, the success rate was significantly low since 10 out of 4,000 embryos were born; a circumstance that some leading stem cell scientists have taken advantage of to describe the controversial experiment as “discouraging”.
The scientists responsible for the experiment claimed not to be clear why the two hybrid piglets died, but since the remaining eight normal piglets that were implanted also died, they believe that it is a problem related to the IVF process rather than the fact of having created a chimera in the laboratory, since IVF is a notoriously complicated procedure in pigs.
Ethical concerns
Despite the research, some members of the scientific community have warned against the creation of chimeras due to ethical concerns, as many fear that in the case of stem cells (human, since the objective is that they serve as harvesters of human organs) they could end in other parts of the animal or even in its brain, with unintended consequences.
The research is part of a continuous effort to develop animals, be they sheep or pigs, that can produce human organs that we can then harvest for transplants. Human stem cells can renew and regenerate, making them potentially capable of generating human organs in mammals for future transplantation through a process called xenogenesis. The tests with mice have been relatively successful in the production of chimeric organisms, but the method is much more complex in humans for many reasons (biological, ethical …).
The scientists plan to try again, increasing the proportion of chimeric cells (if that works, they will try to create pigs that are born with a complete organ made up of primate cells) . And they believe their data can help other scientists working in the same field. “We believe that this work will facilitate the development of xenogenic organogenesis by providing a better understanding of the processes of xenogenic recognition, fate determination, and proliferation and differentiation of primate stem cells during porcine development. Our findings could pave the way to overcome the obstacles in reengineering heterogeneous organs and achieving the ultimate goal of reconstruction of human organs in a large animal , “the authors conclude.
Fun fact: Chimerism is naturally extremely rare in humans. There are fewer than 100 documented cases, including a 1953 report published in the British Medical Journal in which the finding of a woman with two types of blood group was exposed, due to the cells of her twin brother that live in her body.
Reference: Rui Fu, Dawei Yu, Jilong Ren and Chongyang Li have contributed equally to this work. Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs. Protein Cell 2019. First Online: November 28, 2019 DOI: https://doi.org/10.1007/s13238-019-00676-8
