What are blastoids, roles in biomedical research, & ethical considerations

Blastoids are lab-grown models of human embryos that represent a relatively new area of developmental biology research.

The goal of today’s post is to give you everything you need to know about this topic.

What’s in this article

What are blastoids? | How are blastoids made? |  Use in research | Blastoids challenges & Ethics Questions | Looking AheadReferences

Human embryo model research has taken off in the past few years. It could positively impact medicine in the long run. The outcomes could include advances in understanding and approaching infertility and birth defects. However, at the same time embryo models raise complicated policy and ethical questions. There are also technical challenges.

blastoids nature paper figure 2
A human blastoid with immunofluorescence co-staining images of ZO1 (Zonula Occludent-1, green) and phalloidin (red). Blue, nucleus.  Blastoids Nature paper, Figure 2, 2021.

I’ve been doing more reading on this technology. It feels more pressing to understand it better. My own research has raised the prospect of potentially making human blastoids in the future in my lab.

What are blastoids?

Blastoids are a relatively simple model version of a human embryo made from stem cells.

These models go by several names including both blastoids and iblastoids as well as gastruloids.

For simplicity I’ll just focus on blastoids and use that nomenclature. (Note that there is another use of the term blastoid to mean some specific extinct species of echinoderms. In this post we are focusing on blastoids as embryo models.)

These models can end up resembling blastocysts, a human embryo stage where there are about 100 cells.

How are blastoids made?

A variety of protocols have been reported for making human embryo models, generally starting with human pluripotent stem cells.

The protocol triggers coherent, sequential differentiation stages in specific ways by changing the media sequentially. You can see a video article of a typical protocol for making human blastoids. In the last few years, researchers have been able to make human embryo models that are far more similar to the real thing.

However, in the past, the embryo models weren’t that close to the real thing.

For instance, a common, very basic mass of embryonic tissue made from pluripotent stem cells like iPS cells is called an embryoid body. It’s not very similar to actual human embryos, but still very useful. However, in recent years, the technologies to make models including blastoids have become more sophisticated. As a result, the embryo models are much more similar to the real thing. Human blastoids can look very similar to human blastocysts made by IVF.

Use of human embryo models in research

Human embryo models are powerful tools to better understand early human development.

As I’ve written before, it’s remarkable how little we know about very early human development as compared to that of the fruit fly or the laboratory mouse or rat. We need to understand early human development better to address a variety of human conditions. For example, to come up with new preventative measures for certain birth defects, we need to know what causes them and how. Embryo models can help in this area.

In addition, embryo models are powerful ways to advance our understanding of the basic mechanisms of normal human development. What do certain genes do in a 3, 4, or 5-day-old human embryo? We often aren’t sure and just assume the same functions as in mice. In this area, embryo models can fill in the human-specific gaps.

Challenges and ethical considerations

The main research challenge is to try to make human embryo models as similar to the real thing as possible. The more resemblance to a real human embryo, the more impactful the research might be. At least that’s how it seems at first glance.

On the other hand, as human embryo models like blastoids get ever closer both in form and maybe function to real human embryos, the research may start to get more ethically thorny.

One of the biggest questions for me is at some point how we would know whether a lab-produced human blastoid is equivalent to the real thing? If put into a surrogate mother would it develop into a fetus and then if things continue what happens? I don’t expect anyone to talk about implanting blastoids into surrogate mothers to try to make babies. At least not any time soon. Short of that, can we ever be sure whether a blastoid is basically no different than a real embryo?

Looking ahead

Blastoid research in non-human primates is ongoing. Someone could bring those embryos to term and see how they turn out. That’s not the same thing though as learning what would happen with implanted blastoids.

Technologies continue to advance in growing actual human and other types of embryos in the lab for much longer periods. In that context, it’s not impossible to think that someone could accidentally or because of hubris try to take human blastoids further to the point that they are early human fetus models.

This seems extremely unwise to me, yet it has been mentioned.

The fact that the leading international stem cell research society, ISSCR, pulled back somewhat from a strict limit called the 14-day rule on human embryo growth in the lab creates more risk in my view. Reckless human embryo model research, for instance, culturing the models far too long in the lab, risks damage to the field.

I know some of the labs doing research in this area and they are very responsible, which is reassuring. However, others are not so careful. They don’t seem to engage in the needed thoughtful considerations in advance for this kind of research.

Hopefully the dialogue on blastoids and other human embryo models will continue in parallel to the research advances.

References

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