An international team of researchers led by the Weizmann Institute of Science in Israel has recently developed human embryo models using lab-cultured stem cells, providing an unprecedented view of the critical first week post-implantation into the uterine lining.
A deeper insight into the moments right after a fertilized egg embeds itself in the womb’s lining can enhance our understanding of fertility, early pregnancy loss, and congenital birth anomalies. However, ethical and logistical barriers have limited scientists’ grasp on these vital phases of human embryonic progression.
“The drama is in the first month, the remaining eight months of pregnancy are mainly lots of growth,” explained senior author Jacob Hanna, a molecular geneticist at Weizmann. “But that first month is still largely a black box. Our stem cell–derived human embryo model offers an ethical and accessible way of peering into this box.”
The experts prompted genetically untouched, unspecialized stem cells from humans to form intricate configurations that simulate human embryonic growth.
This procedure uncovers the amazing innate structuring capability of human stem cells. It builds on a recent advancement in creating embryonic-like stem cells. The procedure also grants scientists a fresh avenue to explore aspects that were poorly understood until now due to logistical and moral dilemmas.
This approach highlights features not found in earlier models, such as the three lineages that construct the placenta and embryonic support systems, as well as the cellular layer that shapes an embryo before its internal folding and differentiation into various tissues and organs.
Earlier studies indicated that stem cells extracted from mouse embryos can still be externally directed to develop into tissues that sustain and constitute the embryo. They naturally assemble into a structural stem-cell based embryo model (SEM) post-gastrulation. In this stage, embryonic cells transform into three main types of body tissue.
“Here, we extend these findings to humans, while using only genetically unmodified human naïve embryonic stem cells,” the scientists explained. “We proceeded to test the capacity to form embryo-like structures […] that could mimic different stages of natural human in utero development.”
The experts further determined the ideal conditions – such as cell counts, relative proportions within cell blends, and culture compositions for different phases – starting from the implantation, which takes place roughly seven to eight days post-fertilization.
“These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization,” the researchers wrote.
The models illustrate the construction of every recognized segment of early human embryos. These include the epiblast, hypoblast, extraembryonic mesoderm, trophoblast, and yolk sac.
Researchers observed that cell data from the human SEMs aligned with gene expression patterns and cell types in human embryos soon after implantation. This, when compared to a reference data set. While human SEMs don’t mirror embryos perfectly, they can open new, valuable pathways for future investigations.
“Many failures of pregnancy occur in the first few weeks, often before the woman even knows she’s pregnant. That’s also when many birth defects originate, even though they tend to be discovered much later,” Hanna explained.
“Our models can be used to reveal the biochemical and mechanical signals that ensure proper development at this early stage, and the ways in which that development can go wrong.”
The scientists hope that these findings will facilitate deeper investigations into early human development, as well as into issues related to infertility and the growth of tissues for transplants.
“This research and other recent reports on models of the early human embryo show that models are getting more sophisticated and closer to […] normal development, highlighting that a robust regulatory framework is more needed than ever before,” concluded Darius Widera, a professor of Stem Cell Biology and Regenerative Medicine at the University of Reading.
Stem cells have often been hailed as the superheroes of the cellular world. They hold incredible potential for regenerative medicine and tissue engineering. These unique cells serve as the foundation of our body’s cellular machinery. They have the ability to both replicate themselves and transform into specialized cells.
At the heart of every organ and tissue in our body, stem cells play a pivotal role. They are undifferentiated cells that can both self-renew (make copies of themselves) and differentiate (become specialized cells, like heart, brain, or liver cells). This dual capability is what sets them apart and makes them so valuable in the realm of medical research.
Embryonic Stem Cells (ESCs): Derived from the inner cell mass of a blastocyst (an early-stage embryo), these cells are pluripotent. This means they can become any cell type in the body.
Adult or Somatic Stem Cells: Present in various tissues throughout our lifetime, these cells usually differentiate into cell types of their tissue of origin. For example, hematopoietic stem cells in the bone marrow create different blood cells.
Induced Pluripotent Stem Cells (iPSCs): Scientists can now revert mature cells (like skin cells) back to a pluripotent state, essentially giving them similar capabilities as ESCs. This revolutionary discovery opened a world of potential, as it provides a way to get pluripotent cells without using embryos.
Stem cells hold the promise of a host of treatments. Here are some of the ways researchers are harnessing their power.
Regenerative Medicine: We can use stem cells to replace damaged or diseased tissue. This ability will potentially revolutionize treatments for conditions like heart disease, diabetes, and spinal cord injuries.
Drug Testing: Before testing a new drug on humans, researchers can use stem cells to predict its safety and efficacy.
Disease Modeling: By creating stem cell models of genetic diseases, scientists gain a deeper understanding of these conditions and can search for potential treatments.
While the potential of stem cells is undeniable, their use, especially ESCs, comes with ethical concerns. Since ESCs come from embryos, this raises questions about the moral status of the embryo and the right to life.
However, the advent of iPSC technology offers a promising path that sidesteps many of these ethical issues. With ongoing research and collaboration, we can continue to unlock the mysteries and potentials of stem cells, aiming for a future where the marvel of regeneration is within our grasp.
The study is published in the journal Nature.
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