Scientists create first living models of human embryos

Scientists have for the first time grown living reproductions of human embryos in the laboratory – with all the cell types, biochemical activity and overall structure of real embryos.

The research, which aims to help understand problems that cause miscarriages and birth defects, could raise fears about a slippery slope to human genetic engineering and cloning.

But scientists doing research at Monash University in Australia and the University of Texas in the US say their creations, called blastoids, are not perfect replicas of real embryos and are not suitable for implantation in the womb.

The research teams reported in the journal Nature on the creation of blastoids – cellular compounds that resemble blastocysts, the stage of embryonic development five to ten days after an egg is fertilized.

For ethical reasons, there is an internationally accepted limit of 14 days on growing human embryos for research and so far, scientists working on living models such as blastoids have observed the same limit.

The International Society for Stem Cell Research, the professional body of the field, aims to address ethical issues by soon issuing new guidelines for creating embryos from stem cells.

“Blastoids will enable 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, more importantly, on an unprecedented scale, accelerating our understanding and development of new therapies, ”said Jose Polo, leader of the Monash Project.

Both teams grew their blastoids from stem cells – derived by reprogramming adult cells or extracting them from embryos. The cells were treated with biochemical cocktails and cultured in laboratory dishes containing a culture medium designed to allow them to develop like real embryos.

After being cultured for a week or so, the cells became blastoids of the same size and shape as natural blastocysts. They contained more than 100 cells that began to differentiate into the different cell types that would later produce different tissues in an older fetus.

Some of the blastoids implemented behavior in the uterus as it was attached to the culture dish and allowed new cells to grow that could develop into a placenta.

The scientists insisted that, although blastoids would be very valuable in studying what happens at the beginning of pregnancy, they should not be considered as synthetic embryos. “There are a lot of differences between blastoids and blastocysts,” said Texas team leader Jun Wu. “Blastoids will not be viable embryos.”

Last June, Naomi Moris and colleagues at the University of Cambridge published groundbreaking work on a later phase of embryonic development. Her laboratory bypassed the earlier developmental stages suggested by blastoids and produced simplified models of older (18 to 21 days) embryos.

“This is a very exciting time for human embryology,” said Moris, who moved to the Crick Institute in London. “New instruments and stem cell technology deliver an influx of embryo-like models, giving us the opportunity to understand how we evolve from a single cell to a complete human being.”

In May, the international ISSCR watchdog will issue new ethical guidelines for the growth of embryo models based on stem cells – ‘stem embryos’, as some call them. “Research using these models has the potential to understand a period of development often referred to as the ‘black box,'” said Professor Amander Clark of the University of California, Los Angeles. He works with the task force of the association to update the research guidelines.

“The models have the potential to improve infertility treatments and interventions for congenital heart and brain defects and other genetic diseases,” she added. “As these models continue, research review committees will need a set of criteria to review the admissibility of research proposals.”

Meanwhile, research on the artificial reproduction of mice, unbounded by ethical issues, has moved much further. Scientists from the Weizmann Institute in Israel reported in the same issue of Nature that mouse embryos have been growing healthy for 11 days – just over half of their normal gestation period – in an artificial uterus or womb.

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