A recent study reports the generation of a fetus and a chimeric monkey born alive using homologous pluripotent cells of embryonic origin (ESC), in which up to 90% of chimeric cells have been obtained in some tissues.
The experiment was carried out in the Laboratory of Primate Neurobiology of the Chinese Academy of Sciences, in Shanghai. Dr Miguel Ángel Esteban’s group has collaborated with the teams of his colleagues Qiang Sun and Zhen Liu. In this sense, Dr. Esteban’s team already announced two months ago the generation of a partially humanized kidney in a pig embryo, in an experiment that must be bioethically evaluated given the difficulties it presents.
Firstly, the technique consists of obtaining pluripotent cells from seven-day-old embryos that were cultured in the laboratory. Subsequently, after marking these cells with a fluorescent protein that allowed their subsequent localization, they inoculated them into four-day-old monkey embryos.
Among the 12 pregnancies, 4 aborted fetuses and 6 full-term live offspring were obtained. Unborn fetuses and born monkeys were analyzed to determine the level of contribution of the stem cells to the host or recipient individual.
One of the monkeys that was born alive and a fetus that suffered a spontaneous abortion were confirmed to be substantially chimeric, containing cells derived from the other monkey’s stem cells throughout their bodies. This was confirmed by the presence of fluorescence and by genetic sequencing.
Both individuals were males. After surviving for 10 days, the chimeric monkey’s health condition deteriorated with respiratory failure and hypothermia and it was euthanized.
This chimerism, consisting of the presence of pluripotent cells from another monkey embryo, occurred in the brain, heart, kidneys, liver and other organs: between 21% and 92%, depending on the tissue.
The high percentage of chimerism obtained in some tissues, considered by researchers as a success, is due to the optimization of the culture conditions for pluripotent embryonic cells (ESC) and the protocol for the subsequent culture of embryos in vitro.
The generation of live chimeric monkeys with homologous ESCs provides an approach that may be useful for the production of monkey models with sophisticated genetic modifications for basic and translational research.
Recently developed gene editing technologies applied in zygotes make it relatively easy and efficient to achieve accurate gene targeting results in embryos of multiple species, including macaque monkeys.
However, more complex gene editing techniques, such as insertion or replacement of large fragments and targeting of genes at multiple locations, remain very difficult.
An alternative that is proposed is the cloning of monkeys through nuclear transfer of somatic cells, although it offers low efficiency. According to scientists, obtaining this type of chimera would allow specimens to be designed with certain alterations to be used as an object of study. This would be possible by introducing gene-edited chimeric pluripotent cells to reproduce diseases or test the effect of modifying or deleting certain genes.
The possibility of these findings being translated into real clinical applications is still a long way off. The low efficiency of the techniques and the complexity of the related gene editing processes pose serious safety problems and mean that this type of chimeric experiments in animals must be greatly improved.
Its transfer to humans, as has already been experienced on previous occasions with monkey-human chimeras, is much more complex and raises serious ethical dilemmas that must be taken into account. The difficulty of determining what degree of colonization with human cells the chimeric embryo produced reaches can undoubtedly raise ethical problems that are difficult to solve.
Due to this, it may not be ethical to generate and manipulate these chimeras, much less destroy them, as there is the possibility that said colonization extends beyond the organ that is intended to be produced and may even reach the brain or gametes.
Julio Tudela and Lucía Gómez Tatay
Bioethics Observatory – Institute of Life Sciences
Catholic University of Valencia