Embryonic development, also known as embryogenesis, is a cornerstone of understanding the origins of life. But studying this complex and layered marvel of biological processes in humans faces significant challenges. Early stage human embryos are difficult to obtain. There are also ethical issues surrounding their use. This has made it difficult for scientists to understand early human development.
However, advances in genetic engineering and molecular and cellular biology have catalyzed the emergence of synthetic embryology, a subfield dedicated to replicating and studying embryonic development in a petri dish using human stem cells. Synthetic embryology could help researchers overcome the challenges of using real human embryos by providing new tools for exploring the mysterious early stages of human development.
As a reproductive and developmental biologist, I develop stem cell models for embryogenesis. With these new models, researchers can better understand conditions that affect human reproduction and development as well as maternal-fetal health, potentially leading to new treatments.
Production of human embryos from stem cells
Embryogenesis begins with the fertilization of the egg. This triggers rapid division of the egg into embryonic cells; These cells soon form an inner cell mass, which eventually develops into an outer cell layer that will form the fetus and placenta.
Upon implantation into the uterus, the inner cell mass develops into three layers that will form all tissues and organs of the human body. Simultaneously, the placenta begins to form as the embryo attaches to the uterine wall; This is a crucial step for the mother-fetus connection. This attachment enables the transfer of nutrients, oxygen and wastes between the mother and the fetus.
Synthetic embryology artificially recreates these developmental stages using human pluripotent stem cells derived from human embryos or induced from adult human cells. Like early embryonic cells, these cells have the ability to develop into any type of cell in the human body. In carefully designed laboratory environments, researchers can coax these cells to form multicellular structures that mimic various stages of embryonic development, including early organ formation.
Researchers created the first human embryo model from embryonic stem cells in 2014. This pioneering model, also called gastruloid, captured important aspects of early human development and showed that scientists could direct pluripotent stem cells to form patterned layers that mirror the three germ layers and embryonic stem cells. outer layers of the embryo.
Gastruloids are easy to propagate and measure when studying early events in development. These 2D gastruloids can also help researchers precisely identify and image embryonic cells. However, this model lacks the complex 3D structure and spatial cell interactions seen in natural embryogenesis.
Advances in human embryo models
Significant advances have been made in this field since the first gastruloid.
Over the years, various models have managed to replicate different aspects of human embryogenesis, such as amniotic sac development, germ layer formation, and body plan organization. Researchers have also developed organ-specific models for early organ development; for example, a model that captures key events of neural development and fetal lung organoids that mimic the lung formation process.
However, none of these models fully covers the entire process of developing a single cell type into the full structure of an entire embryo.
A major breakthrough occurred in 2021, when several research groups successfully used human pluripotent stem cells with higher developmental potential to create blastoids that resemble early-stage embryos prior to implantation. Blastoids form similarly to human embryos, starting from a few cells that proliferate and organize themselves.
The developmental and structural similarity of blastoids to embryos makes them useful for studying the first steps of how embryos form, especially before they attach to the uterus. Blastoids may adhere to laboratory dishes and undergo further growth. They can also mimic embryo implantation in the womb by integrating with the mother’s endometrial cells and developing into later embryonic stages after implantation.
Recently, researchers have successfully created more complex models in the laboratory that mimic what happens after embryos attach to the uterus. Two research teams used specially engineered cells to create structures similar to those of a human embryo about a week after implantation. These models can also create the cells that will develop into sperm and eggs in humans, mirroring what happens in natural development.
Another research group managed to create a similar model from pluripotent stem cells without the need for genetic engineering. This model can even mimic later developmental stages and the beginnings of nervous system formation.
Choosing the right models
In the emerging field of synthetic embryology, no single model can perfectly capture all aspects of embryogenesis. Ultimately, the goal is not to play God by creating life in a petri dish, but rather to enhance our understanding of ourselves. This aim underscores the importance of carefully selecting the model that best suits the particular research objectives at hand.
For example, my previous work focused on chromosomal abnormalities in early human development. Aneuploidy, or cells containing an abnormal number of chromosomes, is a leading cause of pregnancy loss. However, scientific knowledge about how these abnormal cells affect pregnancy and fetal development is very limited.
Because gastruloids can effectively model these aspects of early development, this system may be ideal for studying aneuploidy in early development. It allows researchers to precisely monitor and analyze how aneuploid cells behave and how they affect developmental processes.
Using this model, my team and I discovered that cells with chromosomal abnormalities are more likely to mature into placental cells and are likely destroyed during the development of fetal cells. This finding provides important information about why babies with normal chromosome numbers can be born healthy even in cases of aneuploidy detected during pregnancy. Such discoveries are valuable for the development of diagnostic and prognostic methods in prenatal care.
Future models that better replicate embryonic structures and more closely reflect biological events will not only advance understanding of the fundamentals of early development but also have great potential in solving clinical problems. Researchers can use them to model diseases and develop drugs for early life or genetic conditions. These models are also invaluable for studying tissue formation in regenerative medicine. Creating embryo models from a patient’s own cells could also allow researchers to study the genetics of development and help personalize treatments.
The key to progress in the field of synthetic embryology is unwavering adherence to ethical standards and regulations. Most importantly, these embryo models are neither synthetic nor real embryos. The International Society for Stem Cell Research strictly prohibits the transfer of these embryo models into the uterus of a human or animal. Although these models mimic some features of early developmental stages, they cannot and will not become the equivalent of a human baby after birth. Basing research on sound justification and oversight will help ensure that scientific research into the fabric of life is conducted with the utmost respect and responsibility.
By embracing the complexity and potential of synthetic embryology, researchers stand on the threshold of a new era in biological understanding and are poised to unravel the mysteries of life.
This article is republished from The Conversation, an independent, nonprofit news organization providing facts and authoritative analysis to help you understand our complex world. Written by Min Yang University of Washington
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Min (Mia) Yang receives funding from the University of Washington