Scientists have achieved a remarkable breakthrough in our understanding of early human embryo development by creating human embryo models from stem cells cultured in a laboratory. This achievement provides an unprecedented view of the critical first week after fertilization when the fertilized egg implants into the uterine wall. This research has the potential to shed light on fertility, early pregnancy loss, and developmental birth defects, offering insights that were previously obscured due to ethical and technical challenges.
The study was conducted by an international research team led by molecular geneticist Jacob Hanna from the Weizmann Institute of Science in Israel. Hanna notes that while most of the pregnancy involves growth, the first month is a critical period that remains a “black box” in our understanding of embryonic development. The team’s approach involved coaxing genetically unmodified, undifferentiated human-derived stem cells into complex structures that mimic the process of human embryonic development. This study was published in Nature.
One of the key discoveries of this research is the remarkable self-organizing ability of human stem cells. This builds upon recent breakthroughs in generating embryonic-like stem cells and offers researchers a new and ethically sound way to study early human embryo development. The new model showcases features that were not observed in previous models. It includes the formation of three lineages responsible for the placenta and embryonic support structures. Additionally, it captures the layer of cells that constitute an embryo before it undergoes folding and develops into various tissues and organs.
Previous research has demonstrated that stem cells extracted from mouse embryos could be guided to grow into tissues that support and make up the embryo itself. These stem cells self-assembled into a structural stem-cell based embryo model at the post-gastrulation stage when embryonic cells differentiate into the three primary types of body tissue. In this groundbreaking study, the team extended these findings to humans using genetically unmodified human naïve embryonic stem cells.
The researchers meticulously determined optimal conditions, including cell numbers, cell mixture ratios, and culture compositions for various stages of development, starting from the implantation that occurs 7–8 days after fertilization. This precision allowed them to create human embryo-like structures that mimic different stages of natural human in utero development.
The generated human complete SEMs (structural embryonic models) exhibited developmental growth dynamics that closely resembled key characteristics of post-implantation stage embryogenesis, extending up to 13-14 days post-fertilization. These models faithfully depicted the assembly of all known lineages and components of early-stage human embryos, including the epiblast, hypoblast, extraembryonic mesoderm, trophoblast, and the yolk sac.
Analyses of cell profiles from the human SEMs dataset revealed gene expression patterns and cell type compositions akin to those observed in human embryos shortly after implantation when compared to a reference dataset. It is important to note that while human SEMs are not identical to natural embryos, they serve as a powerful model that opens up significant research opportunities.
Jacob Hanna emphasizes the potential impact of this breakthrough by highlighting that many pregnancy failures occur in the first few weeks, often before a woman even realizes she is pregnant. This early period is also when many birth defects originate, though they may not be discovered until later stages of pregnancy. The newly developed models can be instrumental in uncovering the biochemical and mechanical signals responsible for proper development during this critical early stage, as well as identifying factors that can lead to developmental abnormalities.
The creation of human embryo models from stem cells represents a monumental leap in our ability to study and understand early human embryonic development. This research not only offers profound insights into the intricacies of this critical phase but also provides a promising avenue for investigating the causes of pregnancy failures and birth defects. It is a testament to the power of scientific innovation in addressing complex and challenging questions in the field of human development.
