As we previously explained in an article published by our Observatory, artificial embryos (also called embryoids, embryonic models or blastoids) are cellular aggregates obtained from what are popularly known as “stem cells”. These cells reflect some structures and functions of embryos to a certain degree, and many research teams have been working on them for years in order to study this intriguing and complex stage of our development without having to resort to the use of human embryos, thus avoiding the ethical and legal impediments of these investigations.
Just over a year ago, an article was published in the prestigious scientific journal Nature, in which the authors described the production of an artificial embryo from human stem cells that could be implanted in a kind of artificial womb.
The aim of the research was to generate an artificial embryo model with which to study the complex phenomenon of implantation, the time at which the embryo nests in the mother’s womb, since numerous cases of spontaneous abortions are related to the inability of some embryos to implant successfully.
These artificial embryos have been named blastoids, in reference to the blastocyst, which is the embryo at the stage at which uterine implantation occurs. Different types of human stem cells were used to generate them, including embryonic stem cells (ESCs) and induced pluripotent cells (which are obtained by reprogramming adult cells to a developmental stage comparable to the embryonic one). Similar structures with a comparatively high efficiency were achieved with both cell types, according to the authors of the research. These artificial embryos were brought into contact with a kind of artificial womb, which consisted of a group of endometrial cells lining the inside of the uterus. The researchers found that by adding estrogen and progesterone in the same amount that is produced during pregnancy, the blastoids adhered to the endometrial cells, simulating implantation. The researchers hope that this artificial embryo-uterus model will enable them to study the phenomenon of implantation in greater depth, allowing them to better understand the causes of spontaneous abortions.
With this same objective, the results of the study led by Palestinian scientist Jacob Hanna have also been published in some media recently, albeit not yet in verifiable scientific media. Hanna and his team report that they have managed to imitate one of the least understood phases of embryonic development of a person for the first time. This means having achieved the development of all embryonic structures, unlike previous studies, which is a further step toward human reproduction without fertilization.
In previous paper by the same author, in this case with mice, a newly established platform for prolonged ex-utero growth of natural embryos was adapted to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, from ESCs alone. This was achieved by co-aggregating non-transduced ESCs, with other naïve ESCs transiently expressing the Cdx2 or Gata4 genes to promote their development into the trophoectoderm and primitive endoderm lineages, respectively. The sEmbryos adequately accomplished gastrulation, advanced through key developmental milestones, and developed organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos.
The findings of these studies highlight the plastic potential of naïve pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.
Meanwhile, we have learned of the results obtained by professor of biology and biological engineering at the University of Cambridge and the California Institute of Technology, Dr. Magdalena Żernicka-Goetz, who described her team’s findings in an address last Wednesday at the International Society for Stem Cell Research’s annual meeting in Boston, according to British newspaper The Guardian.
Dr. Żernicka-Goetz claimed that they could “create human embryo-like models by the reprogramming of [embryonic stem] cells,” which distinguishes this experiment from Dr. Hanna’s, since in this case, a genetic modification of the ESCs used was performed.
She had previously published their experiments with mice, also aimed at obtaining embryoids that complete the gastrulation phase and progress in their evolution toward early organogenesis.
They also claim that not only can pseudoembryos be obtained by this procedure, but that germ cells, oocytes and spermatozoa could also be derived using this method. This possibility is also part of attempts to achieve human reproduction by bypassing sexual reproduction.
First of all, in both experiments, both Hanna and Żernicka-Goetz’s, ESCs are taken from human embryos usually left over from assisted reproduction procedures, from which pluripotent stem cells are extracted, requiring their destruction.
Second, Dr. Hanna claims not to have genetically modified them, but has actually subjected them to chemical stimuli to achieve the development of all the embryonic structures, which can lead to epigenetic changes that condition gene expression in the embryo. In the second paper, Dr. Żernicka-Goetz’s, there is gene editing of the ESCs used, in order to achieve the development of embryonic and extraembryonic structures. Accordingly, this latter experiment merits the same negative bioethical consideration as in the previous case, with the added difficulty that genetic manipulation of the precursor cells of the embryo was performed, with unpredictable consequences in the hypothetical future that its development until birth was pursued.
Third, the embryos produced are human, they are generated to be destroyed. The argument that they cannot develop until birth is not sufficient to disregard them as individuals of the human species. Since they share human genetic makeup and show the ability to develop in their early evolutionary stages, it is very difficult to establish what degree of differences with human embryos obtained by fertilization must be found to classify them as true embryos or, on the contrary, as pseudoembryos, embryoids, blastoids or embryo-like models.
According to the principle of prudence, as long as this question remains unresolved, they should be treated as human until these differences are sufficiently evident to include them in one or other classification. All this supports the bioethical rejection of their production in the current circumstances.
It is important to note that these findings have not yet been officially published in scientific journals, so the precise details of these investigations — necessary for a more exhaustive evaluation — are not known.
Julio Tudela and Lucía Gómez Tatay
Institute of Life Sciences – Bioethics Observatory
Catholic University of Valencia