Stem cells make human embryos without sperms and eggs

Stem cells make human embryos without sperms and eggs.

On June 15, 2023, research teams led by developmental biologist Magdalena Zernicka-Goetz from the University of Cambridge in the UK and stem cell biologist Jacob Hanna from the Weizmann Institute of Science in Israel published their research papers on the preprint platform bioRxiv .

In these two papers, the research teams announced that they have cultured embryo-like structures made entirely of human stem cells, which are more advanced than any previous research. The artificially synthesized embryos cultured by them developed to a stage equivalent to natural embryos in about 14 days.

On June 27, 2023, the research by Magdalena Zernicka-Goetz’s team titled: Pluripotent stem cell-derived model of the post-implantation human embryo was published in the journal Nature .

On September 6, 2023, the research by Jacob Hanna’s team titled: Human blastoids model blastocyst development and implantation was published in the journal Nature .

These two achievements provide unprecedented opportunities for studying the later stages of human embryonic development, but they also raise new controversies about how to define the “identity status” of these artificially synthesized embryos and how to regulate their ethical and legal issues.

How are these two studies different from previous embryonic research?

In August last year, these two teams published papers in the journals Nature and Cell , respectively. They both used similar techniques to create embryo models from mouse cells. These embryo models developed to the stage where organs such as the heart and brain began to form. But no research has been able to do this in human embryo models.

In these two latest studies published in Nature, the research teams created embryo-like structures that can self-assemble from human embryonic stem cells, some of which have been transformed into cell types similar to those that form the placenta and form outside of natural developmental embryos. The yolk sac.

The research teams said that the resulting artificial synthetic embryo models showed structures (during and after gastrulation, when the cells that form the embryo are organized into a layer between the amniotic cavity and the yolk sac) and gene transcription profiles found in human embryos 6-14 days after fertilization.

The research teams said that this is the most advanced human embryo model to date.

What is the significance of embryos surviving for 14 days?

Research on natural human embryos often requires compliance with a widely adopted guideline that human embryos should not be cultured in laboratories for more than 14 days. This guideline is legally enforced in many countries. This means that if you want to study the later stages of embryonic development, you must use animal embryos, and animal embryonic development may not necessarily reflect the corresponding processes of human embryos.

In most countries, embryo models are not defined as natural embryos, so they are not subject to the 14-day rule.

This means that you can use this artificial synthetic embryo model to culture it in a laboratory for more than 14 days, thereby studying the later stages of human embryonic development and solving the ethical and technical challenges faced by using natural human embryos for research.

Why are these two studies controversial?

Culturing embryo models to later stages of development has become a highly competitive scientific research race, which also brings many arguments and controversies.

Whether these two new studies published on preprints can ultimately pass peer review remains to be seen. For example, some developmental biologists believe that the artificial synthetic embryos described in the paper have nothing that can be considered similar to real 14-day embryos. They only see a lot of cells separated into small chambers without any embryonic-like tissues.

Magdalena Zernicka-Goetz, one of the corresponding authors of one of the papers, said that this embryo model still has limitations in studying development and cannot generalize all aspects of natural embryos. It is used as a supplementary tool for studying specific tissue differentiation at key developmental stages.

Still facing ethical issues

These two new studies have sparked a discussion about the “identity status” of human embryo models and a controversy over whether they should continue to be outside of human embryonic legislation.

In fact, although embryo models are not subject to the 14-day rule, the embryo-like structures constructed by the two research teams do need to comply with guidelines and regulations on the use of human embryonic stem cells. And other teams use embryo models created from induced pluripotent stem cells derived from adult somatic cells, which can be free from these rules.

So far, no one has made an embryo model that can develop into a human. And a recent study on primate embryo models showed that implanting monkey embryo models into the uterus can induce pregnancy (but it will end naturally shortly after pregnancy).

This study came from Liu Zhen and Sun Qiang’s team from the Center for Brain Science and Intelligent Technology of the Chinese Academy of Sciences and Zhou Fan’s team from the School of Life Sciences of Tsinghua University. It was published in the journal Cell Stem Cell on April 6, 2023 . The study used embryonic stem cells to establish a crab-eating monkey blastocyst induction system. The in vitro culture of crab-eating monkey blastocysts can induce gastrulation-related germ layers, and in vivo transplantation can detect the appearance of early pregnancy sacs.

Therefore, some researchers believe that the definition of embryos needs to be modified to clarify these issues. For now, the sole purpose of embryo models is to avoid the current restrictions on embryonic research. And whether the 14-day rule should continue to be adhered to has also become a topic worth discussing.

Paper links:

1. https://www.biorxiv.org/content/10.1101/2023.06.15.545082v1
2. https://www.biorxiv.org/content/10.1101/2023.06.14.544922v1
3. https://www.nature.com/articles/s41586-023-06368-y
4. https://www.nature.com/articles/s41586-023-06604-5
5. https://www.nature.com/articles/s41586-022-05246-3
6. https://doi.org/10.1016/j.cell.2022.07.028
7. https://doi.org/10.1016/j.stem.2023.03.009

Stem cells make human embryos without sperms and eggs