Reacción a "Reactions: First chimeric monkey born from embryonic stem cell lines"

In this study, the authors report the birth of monkeys with a high degree of somatic chimerism from the fusion of embryonic stem cells with a blastocyst [an embryo at 5 or 6 days of development after fertilisation]. A chimera is an organism composed of cells with different genetic identities. This work represents an important milestone in mammalian developmental biology, particularly that of primates and, by extension, human biology. 

Embryonic stem cells (ESCs) represent a source of important applications for fundamental biology and biomedicine. The fundamental property of these cells is their pluripotency, their ability to contribute to all the organs of an organism, something that is tested with chimeras. This technique was fine-tuned in mice. Cells are put into a blastocyst where they are mixed. The blastocyst is implanted and allowed to develop, the result is a mouse in which all the tissues are a mixture of the two kinds of cells. So, for example, if cells from a black mouse are used with the blastocyst from a white mouse, the mouse will have a random mixture of the two cell types and will have a mixture of black and white fur.  

In the case of humans, this experiment is not possible and other techniques are used to test the pluripotency of the cells, such as the generation of teratomas (benign tumors with cells from multiple tissues) in mice which, although approximate, are not the same. For this reason, the pluripotency of human embryonic cells does not yet have reliable proof. 

The last ten years have seen great advances in the use of these cells with the development of several protocols leading to the generation of a wide variety of organs and tissues in vitro from ESCs. However, in the case of humans, proof of their pluripotency through chimeras is still lacking. If they could be done, these experiments would open the door to the generation of disease models and details of human biology. But, of course, the experiments are not ethically possible. 

Non-human primates offer an alternative possibility, because - although under the control of strict ethical standards, and very costly - the experiments would, in principle, be possible. In this paper, a Chinese research group, including the Spaniard Miguel Esteban, report work in this direction. 

The authors obtain embryonic stem cells from cynomolgus monkeys, make them fluorescent and use them to generate chimeras. The chimeras provide a very strong test of the potential of embryonic stem cells and the authors test several methods of growing the cells before doing the experiment. They show that only one of these methods generates cells with the ability to interact with embryonic cells to give rise to an organism. The work is important and has several conclusions that provide valuable information about, and for, the field. 

The first, for me, is that not all embryonic stem cells are the same: depending on the method of isolation and growth, they have different properties. To me this is surprising, and it is important, as [scientists] work with many culture media on the assumption that they are all the same. This work clearly demonstrates that this is not the case. In the most demanding experiment, cells that, from many points of view, look the same are actually not the same. More work will be needed, but this observation is important. The second point that is surprising to me is the low number of chimeras. Starting with 206 experimental embryos, they obtain 6 live births, and some with difficulties then die. The high degree of miscarriages is sobering.   

The good news is that chimeras have been obtained and that we are beginning to know the reasons why a previous experiment in a similar line did not work. The culture medium in which ESCs grow is crucial in determining their status, and only some [media] put the cells in a state that is compatible with embryonic development. 

The work represents a milestone and is rich in detail and clues as to what these ESCs are. It opens the way for the use of nonhuman primates as a model for human biology, for example, in studying the effects of genetic modifications and disease models. But these are not experiments accessible to any biologist. They are very expensive and require special facilities. Also the gestation period and the fact that there is only one baby per mother make it difficult. We will have to wait to see if [this result] goes beyond proof of principle.