“Artificial” Human Embryos ?

Can researchers artificially produce a product resembling a human embryo in a test tube, without using eggs or sperm or undergoing fertilization?

For the past several years, some research laboratories have been experimenting on animal models.

And now experiments are being performed on human cells. Although still being examined, articles 14 and 15 of the pending French bioethics bill, could potentially allow this type of research. These experimental protocols using reprogrammed adult human cells (“iPS” or induced pluripotent stem cells) and human embryonic cells would not necessitate authorization by the Biomedicine Agency, but only a mere declaration, prior to implementation.

Already in 2018, scientists from Cambridge published their initial results, and this week Nature has published the results from two other research labs also working to create in vitro structures called “iBlastoids”. Since these artificially structures are designed to “imitate” human embryos, the name is derived from “blastocysts”, the scientific name given to human embryos at approximately five days old.

The American and the Australian research teams each used different techniques. In Australia, Professor José Polo from Monash University headed the research group working with adult skin cells known as fibroblasts. These cells were reprogrammed to re-acquire their original “pluripotency” (the cell’s ability to differentiate into multiple other cell type and therefore form most body tissues). The resulting induced pluripotent stem cells are commonly abbreviated as iPS cells or iPSCs.

The second group of researchers headed by Jun Wu at the University of Texas, also used iPS cells as well as human embryonic stem cells, harvested from embryos produced by in vitro fertilization (IVF) which had been donated for medical research.

When cultured in adequate conditions, these cells multiply and self-organize into complex cellular structures. For the 3D cell culture system, a support matrix of plastic plates with tiny holes is used to aggregate cells by sedimentation, while controlling their number.

These studies have confirmed that cells “communicate” with each other since they self-organize into cellular structures composed of different cells: a layer of external cells (representing a future placenta, if fertilization and “normal” development were to take place) surrounding a fluid-filled cavity containing a mass of “embryonic” cells.

Nonetheless there are significant differences with naturally occurring structures. For example, the artificial ones contain cells which are not present in real blastocysts. In 2018, French researcher Nicolas Rivron, director of one of the labs at the Austrian Academy of Sciences, succeeded in generating the first mammalian blastocyst structure in a mouse model. However, this specialist estimates that it will take “10 more years to create iblastoids that significantly resemble human blastocysts.”

These structures cannot be sustained for long, thus, at the present stage of research it seems implausible that they could be implanted in a woman’s uterus. Even if experiments progressed that far, the procedure is currently strictly forbidden in France. Experiments have already been performed using the animal model to implant blastoids in the uterus of a mouse. Although the vessels did connect to these pseudo-embryonic structures and the mouse’s immune system interacted with them, there were anomalies observed in these structures as early as four days after implantation.

Those in favor of this research claim that there are several advantages to these experiments. These structures could provide new understanding of the early development of the human embryo. They could also be used as models to test the toxicity of molecules, and for understanding events that occur at the beginning of embryonic development such as spontaneous miscarriages or malformations due to certain drugs or pollutants. The obvious limitation is that they are grown in an artificial environment and are not “normal” embryos.

These experimental models circumvent the ban on creating embryos for research and are presented as an alternative to using supernumerary frozen embryos, especially the model which only uses reprogrammed adult cells. Anyhow, the assumptions made using these models “will need to be validated on human embryos, therefore it will not replace research on embryos donated to science,”  says Teresa Rayon, a biologist at London’s Francis Crick Institute.

According to Hervé Chneiweiss, chairman of the ethics committee at “Inserm” (French National Institute of Health and Medical Research): “this new category of living matter generated by human beings is a grey area” in the legislation.

In the pending bioethics bill in France, section 17 provides for a significant semantic change in Article L. 2151-2 of the Public Health Code. This article currently states that “It is strictly prohibited to perform in vitro embryo conception or clone human embryos for research purposes.” Plans have already been foreseen to add 5 descriptive words to the word “embryo”: “human by the fusion of gametes”. This is a tell-tale sign that the legislation will soon allow research on this type of “embryo” obtained without the fusion of gametes.

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