Scientists have created clumps of human tissue that act like early-stage embryos, a feat that promises to transform research into the first tentative steps of human development.
The clumps of cells, called blastoids, are less than a millimeter in diameter and resemble structures called blastocysts that form within days of an egg being fertilized. Typically blastocysts contain about 100 cells, from which every tissue in the body arises.
Two teams of researchers found that they could make small blastoids from stem cells or reprogrammed skin cells by growing them in 3D wells filled with a broth containing the chemicals necessary for the normal formation of blastocysts.
In separate papers published in Nature, the scientists describe how the cells assemble themselves into spherical blastoids after six to eight days in culture. Tests showed they contain all of the cells seen in natural blastocysts. Some became attached to plastic culture dishes and mimicked the process of implantation in the uterus.
By studying blastoids, scientists hope to learn how newly formed embryos develop leading up to implantation and understand why so many miscarriages occur at this delicate stage of human pregnancy.
Further work will use the cells to understand how certain birth defects may arise and to investigate the impact of environmental toxins, drugs and even viral infections on healthy embryonic development.
“We believe the ability to work at scale will revolutionize our understanding of these early stages of human development,” said Prof. José Polo, who led one of the teams at Monash University in Australia.
Until now, research into the earliest stages of human development has relied largely on couples donating surplus IVF embryos to science. The practice has raised ethical concerns, and limited donations have severely limited progress for scientists. By law, researchers are only allowed to study human embryos until they are 14 days old.
Creating blastoids should overcome these problems by allowing scientists to create hundreds of embryo-like structures in the lab at once.
“We are very excited,” said Jun Wu, an assistant professor at the University of Texas Southwestern Medical Center in Dallas, Texas, and leader of a separate team. “Studying human development is very difficult, especially at this stage of development. It’s essentially a black box. Wu said the blastoids were grown to the equivalent of about day 10 for a human embryo.
Naomi Moris of the Francis Crick Institute in London, who uses stem cells to model human embryo development, called the work important and highlighted the rapid advancements being made in the field. “The excitement of these models is that we can hopefully use them to get a sense of how normal human development is progressing and what processes can play out when something goes wrong, such as miscarriage or birth defects,” she said.
Polo and Wu said that while blastoids were similar to early-stage embryos, they were not identical and could only mimic the first week or so of human development. The approach will not be used to create embryos for implantation, said Amander Clark of the University of California, Los Angeles, who worked with Polo.
But in an accompanying article in Nature, scientists at the University of Michigan suggested that advancements in science would lead to blastoids that mimic human blastocysts better.
The scientists, Yi Zheng and Jianping Fu, wrote, “This will inevitably raise bioethical questions. What should the ethical status of the human blastoids be and how should they be regulated? Should the 14-day rule apply? These questions must be answered before research on human blastoids can proceed with caution. “