THE integral DEVELOPMENT of an embryo outside the uterus – or the possibility of pregnancies outside the maternal body – is no longer just science fiction, but a possibility that today appears more concrete. In Israel, an unprecedented result was achieved at the Weizmann Institute of Science: mouse embryos, extracted from the womb after five days of development, when they were just a pile of cells, passed the 11th day of life in a artificial womb specially designed to supply theembryo of nutrients and oxygen, developing in this new environment all the tissues and organs necessary for adult life.
Embryos of mice grown in artificial wombs
L’artificial uterus, described in a study published in Nature by geneticist Jacob Hanna of the Weizmann Institute, is an appliance which provides – varying them in a calibrated way according to the phase in the development of the embryo – the concentrations of glucose, vitamins, serum, oxygen and Co2 most suitable for the differentiation and formation of tissues and organs. Thus providing the embryo with all that is needed so that it can carry out its wonderful genetic program smoothly. At least until day 11.5 of life, when the mouse embryo is now too large to be able to feed only through the nourishing liquid, and therefore cannot survive in the artificial womb because it cannot reach the formed placenta. the rich maternal blood which is instead present in the uterus.
However, the possibility of studying for such a long period the way in which embryo stem cells differentiate is unprecedented and precious, because it offers new hope of intervening on developmental defects to correct them in time. Also opening the way to perspectives that are both revolutionary and bioethically controversial, such as the idea of artificial embryos, which are not formed – as has always happened since life has existed on Earth – thanks to the union between gametes, but could be produced by appropriately assembling cells taken from the skin and transformed into stem cells.
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Professor Hanna, how did you achieve this?
“It took seven years of work and a lot of patience. And we were lucky to have funds from private donors: this is the only thing that allowed us to carry out an” infinite “project like this one, because it was at high risk of failure. what we understood is that we needed an electronic control device for the administration of nutrients and oxygen: a kind of “ventilation machine” even if it is not for the lungs, but for the environment surrounding the embryo. we had to understand what are the right levels of oxygen, temperature, pressure for each of the different stages of development: for example, at a certain moment you need an oxygen concentration of 13%, in another 20% and so on. we tried different types of incubators, asking ourselves: will the embryo grow better in static or dynamic conditions? “
And so you understood that the ideal ‘artificial womb’ is a rotating structure …
“The rotation prevents the embryo from adhering to the glass walls of the test tube in which it is contained: because if the embryo adheres to the glass instead of floating in the culture liquid, it will develop deformities. After many attempts we were able to do so that the embryo survives for over six days entirely in this machinery, in the most important phase which is that of organ differentiation. We then compared these embryos with those grown normally in the uterus and we found no differences. The embryo does not exceed the 11.5 days of life due to the lack of maternal blood: the next step, for us, will be to find a way to facilitate a blood transfusion through the embryo’s placenta, to continue its development for several days in the artificial womb “.
How do you manage to prevent the embryo from having defects or deformities?
“Emphasizing the self-organizing properties of the embryo. I mean: trying to interfere as little as possible with the embryo while enacting its genetic program. We must just provide the nutrients and the right environment, and let the embryo do its job “.
What prospects are opening up for medicine, thanks to your result?
“As you know, with induced pluripotent stem cells we can take an adult skin cell, transform it into a stem cell and then induce it to differentiate into a cell of any tissue so that we can then transplant it. But today we are limited in our ability to transplant it. effectively guide the differentiation of cells: scientists, in this, try to imitate the embryo. Without succeeding completely. But since the embryo, in fact, is more skilled than scientists in guiding the differentiation of its stem cells, why not let the embryo itself do this work of differentiation? With our approach, this path becomes more viable “.
Can you give us an example?
“If a person needs an organ transplant, one day we will be able to take cells from his skin, transform them into stem cells, group as many as needed to have a” synthetic embryo “, ensure that this (precisely because embryos are more skilled than us scientists in differentiating) begin to differentiate its cells in the various organs and then develop the organ that the patient needs in the appropriate environment. Without risk of rejection because it will be an organ obtained from the patient’s own cells. Obviously this poses the bioethical problem of artificial embryos, and therefore these possibilities will have to be discussed at length “.
What are the prospects for the development of human embryos outside the womb?
“It is too early to tell, although our study opens an interesting way. To date, there are international guidelines that limit the development of human embryos for research purposes (such as research on developmental anomalies) to 14 days. But it seems likely. that in May the ISSCR (International Society for Stem Cell Research) and other organs can extend this limit. For many very important experiments, it would be useful to have 7 or maybe 14 more days. Because this would allow us to study in our artificial environment (where the the way in which the cells differentiate is very visible and therefore perfectly studied, unlike the natural uterus) precisely the most critical phases in the formation of organs, those in which most of the developmental defects occur. Then, of course, there are nations in whose laws prohibit exceeding 14 days. And other countries – such as the United States, United Kingdom, Sweden and Israel – where there is no law on the matter, but development of the embryo beyond 14 days for research purposes is not recommended by bioethics committees. We’ll see if anything changes. “
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