Scientists cultivate complete human embryo model without the use of sperm or egg

The Weizmann Institute team has successfully created an "embryo model" using stem cells, closely resembling a genuine 14-day-old embryo, even demonstrating the release of hormones that registered a positive result on a pregnancy test in the laboratory. The primary aim of developing embryo models is to offer an ethically sound method for gaining insights into the initial stages of human life.

The initial weeks following the fertilization of an egg by a sperm are characterized by profound transformations, evolving from an assembly of vague cells into a form eventually recognizable on a baby ultrasound. This critical period is a significant contributor to miscarriages and birth defects, yet remains poorly understood. As Prof. Jacob Hanna from the Weizmann Institute of Science explains, "It's a black box, and that's not a cliché - our knowledge is very limited."

Embryo research is a complex and contentious subject, involving legal, ethical, and technical challenges. However, there is now a rapidly progressing field dedicated to mimicking natural embryo development.

The Israeli team's research, published in the journal Nature, is being hailed as the first "complete" embryo model, replicating all the crucial structures that emerge in the early embryo. Prof. Hanna states that this model is "really a textbook image of a human day-14 embryo," which has not been achieved before.

Rather than starting with a sperm and egg, the researchers used naive stem cells, which were reprogrammed to possess the potential to develop into any type of body tissue. Chemicals were then employed to encourage these stem cells to differentiate into four types of cells that are present in the early stages of a human embryo:

1. Epiblast cells, which give rise to the embryo proper or fetus.
2. Trophoblast cells, which develop into the placenta.
3. Hypoblast cells, which form the supportive yolk sac.
4. Extraembryonic mesoderm cells.

A precise mixture of 120 of these cells was created, and a small percentage of this mixture spontaneously organized itself into a structure resembling, though not identical to, a human embryo.

Prof. Hanna expressed admiration for the cells' ability to self-assemble, describing it as "an amazing phenomenon." The researchers allowed these embryo models to mature until they resembled embryos 14 days after fertilization, a stage that is legally the limit for normal embryo research in many countries.

Prof. Hanna provided a detailed tour of the embryo model's "exquisitely fine architecture," pointing out features such as the trophoblast enveloping the embryo, the cavities (lacuna) that fill with the mother's blood to transport nutrients to the baby, the yolk sac with functions resembling those of the liver and kidneys, and a bilaminar embryonic disc, a key characteristic of this stage of embryo development.

The hope is that these embryo models will facilitate the understanding of how various cell types emerge, enable observation of the earliest stages of organ formation, and provide insights into inherited or genetic diseases. Already, the study has shown that certain parts of the embryo will not develop unless the early placenta cells surround it. There is also potential for improving in vitro fertilization (IVF) success rates by uncovering reasons for embryo failure or testing the safety of medications during pregnancy using these models.

While acknowledging the promise of these embryo models, Prof. Robin Lovell-Badge, an expert in embryo development at the Francis Crick Institute, emphasizes the need to address the current 99% failure rate. Understanding the causes of miscarriages or infertility would be challenging if the model fails to self-assemble most of the time.

Additionally, the research raises questions about the possibility of extending embryo development beyond the 14-day stage. This would not violate the law, even in the UK, as embryo models are legally distinct from actual embryos. However, opinions on this matter vary among experts and the public.

Prof. Alfonso Martinez Arias from Pompeu Fabra University lauds the research as "a most important piece of research" that has achieved the faithful construction of the complete structure of a human embryo from stem cells in the lab, opening doors for studying the events leading to the formation of the human body plan.

The researchers emphasize that it would be both unethical and illegal to attempt pregnancy using these embryo models since assembling the 120 cells surpasses the point at which an embryo could successfully implant into the uterine lining.