First model of early human embryo generated from skin cells
In a discovery that will revolutionize research into the causes of early miscarriage, infertility and the study of early human development - an international team of scientists led by Monash University in Melbourne, Australia has generated a model of a human embryo from skin cells.
The team, led by Professor Jose Polo, has successfully reprogrammed these fibroblasts or skin cells into a 3-dimensional cellular structure that is morphologically and molecularly similar to human blastocysts. Called iBlastoids, these can be used to model the biology of early human embryos in the laboratory.
The research, published today in Nature, was led by Professor Polo, from Monash University’s Biomedicine Discovery Institute and the Australian Regenerative Medicine Institute, and includes first authors Dr Xiaodong (Ethan) Liu and PhD student Jia Ping Tan, as well as the groups of Australian collaborators Dr Jennifer Zenker, from Monash University and Professor Ryan Lister from the University of Western Australia and international collaborators, Associate Professor Owen Rackham from Duke-National University of Singapore and Professor Amander Clark from UCLA in the United States.
The achievement is a significant breakthrough for the future study of early human development and infertility. To date, the only way to study these first days has been through the use of difficult to obtain, and scarce, blastocysts obtained from IVF procedures.
The Polo Lab succeeded in generating the iBlastoids using a technique called “nuclear reprogramming” which allowed them to change the cellular identity of human skin cells that - when placed in a 3D ‘jelly’ scaffold known as an extracellular matrix - organized into blastocyst-like structures which they named iBlastoids.
iBlastoids model the overall genetics and architecture of human blastocysts, including an inner cell mass-like structure made up of epiblast-like cells, surrounded by an outer layer of trophectoderm-like cells and a cavity resembling the blastocoel.
In human embryos the epiblast goes on to develop into the embryo proper, while the trophectoderm becomes the placenta. However, "iBlastoids are not completely identical to a blastocyst. For example, early blastocysts are enclosed within the zone pellucida, a membrane derived from the egg that interacts with sperm during the fertilisation process and later disappears. As iBlastoids are derived from adult fibroblasts, they do not possess a zona pellucida” he said.
An iBlastoid is not generated using an egg or sperm, and has limited ability to develop beyond the first few days.
The lead author on the Nature paper, Dr Xiaodong (Ethan) Liu, a post-doctoral researcher in the Polo Lab, said: “Only when all the data came together and pointed to the same place, could we believe that we had made such a discovery.”
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