Scientists have grown what they say are the first living models of early human embryos that include all the cell types, the biochemical activity and the overall structure of natural embryos.
Two research projects, carried out at Monash University in Australia and the University of Texas in the US, are intended to help understand developmental problems that can cause miscarriages and birth defects.
The scientists say their creations, called blastoids, are not perfect replicas of real embryos and are not suitable for implantation into a womb. But for some they may raise again old fears of a slippery slope towards human genetic engineering and even cloning, facilitated by advances in stem cell technology.
The International Society for Stem Cell Research, the field’s professional body, aims to address some of these ethical fears by issuing new guidelines soon for creating embryos from stem cells.
The Monash and Texas teams reported in the journal Nature their creation of blastoids — cellular assemblies resembling blastocysts, the stage of embryonic development five to 10 days after an egg has been fertilised.
“Blastoids will allow scientists to study the very early steps in human development and some of the causes of infertility, congenital diseases and the impact of toxins and viruses on early embryos — without the use of human blastocysts [from IVF] and, importantly, at an unprecedented scale, accelerating our understanding and the development of new therapies,” said Jose Polo, leader of the Monash project.
Both teams grew their blastoids from stem cells — derived either by reprogramming adult cells or extracted from embryos. The cells were treated with biochemical cocktails and grown in lab dishes containing a culture medium designed to make them develop like real embryos.
After being cultured for a week or so, the cells had become blastoids of a similar size and shape to natural blastocysts. They contained more than 100 cells which were beginning to differentiate into the various cell types that would later produce different tissues in an older foetus.
Some of the blastoids showed behaviour mimicking implantation into the uterus, as they attached to the culture dish and grew new cells that could develop into a placenta.
The scientists insisted that, although blastoids would be very valuable for studying what happens at the start of pregnancy, they should not be regarded as synthetic embryos. “There are many differences between blastoids and blastocysts,” said Jun Wu, leader of the Texas team. “Blastoids would not be viable embryos.”
Last June Naomi Moris and colleagues at the University of Cambridge published groundbreaking research on a later phase of embryonic development. Her lab bypassed the earlier development stages represented by blastoids and produced simplified models of older (18 to 21-day) embryos.
“This is a very exciting time for human embryology,” said Moris, who has just moved to the Crick Institute in London. “New tools and stem cell technology are producing an influx of embryo-like models, which give us a chance of understanding how we develop from a single cell into a full human being.”
For ethical reasons there is an internationally accepted 14-day limit on growing human embryos for research and so far scientists working on living models such as blastoids have observed the same limit.
In May the International Society for Stem Cell Research is due to issue new ethical guidelines for growing embryo models based on stem cells — “stembryos” as some are calling them. “Research using these models has the potential to understand a developmental period often referred to as the ‘black box’,” said Professor Amander Clark of the University of California Los Angeles, who is on the society’s task force updating research guidelines.
“The models have the potential to improve treatments for infertility and interventions for congenital heart and brain defects and other genetic diseases,” she added. “As these models continue to advance, research review committees will need a set of criteria for reviewing the permissibility of research proposals.”