Scientists create human embryo-like model from stem cells and skin

He always little access that exists in medicine for human embryos being studied has hampered research on human embryogenesis and many of the problems that arise in early pregnancy.

Understanding early pregnancy loss and getting information about early developmental defects is key to this milestone in men. For that, two different groups of scientists have worked for years to create blastocyst-like structures from human stem cells.

Blast cells are a phase in the development of the mammalian embryo, equivalent to the blastula, which is a complex cellular structure derived from the morula; It is made up of an internal cell mass from which the embryo originates and a peripheral layer of cells that will form the placenta.

According to the teams of University of Cambridge and Hubrecht Institute in the Netherlands, this pseudo-embryo model makes it possible for the first time to directly observe the processes underlying the formation of the human body. It is the first time that human stem cells have been used to create a three-dimensional model of the human embryo, after those made with mouse and zebrafish stem cells. The developed prototype partly resembles an 18-21 day old embryo.

Both scientific studies were published in the prestigious journal Nature. In the first study, the researchers presented the development of human pluripotent stem cells that provide an alternative way to study human development in the laboratory.

Recent advances in partial embryo models derived from human pluripotent stem cells have made it possible to examine human development in the early post-implantation stages. However, Preimplantation human blastocyst models lacking to study. From naive human pluripotent stem cells, specialists have developed an efficient three-dimensional culture strategy with successive differentiation of the lines and self-organization to generate blastocyst-like structures in vitro.

“Our model shows part of the human map. It is exciting to witness the development processes which until now have been hidden from view and study, ”he said. Alfonso Martínez-Arias, professor at the University of Cambridge in Great Britain, who co-led the project. “The hope is that understanding these processes will reveal the causes of birth defects and diseases in humans, and may lead to the development of tests related to these abnormalities or diseases in pregnant women», Underlined the expert.

The doctor Daniel A. Schmitz, one of the authors of the scientific study said that “these structures, which we call human blastoids, resemble human blastocysts in terms of morphology, size, number of cells and the composition and assignment of different cell lines. Single-cell RNA sequencing analyzes also reveal the transcriptomic similarity of blastoids to blastocysts. Human blastoids are sensitive to the derivation of embryonic and extraembryonic stem cells and can then develop into peri-implantation embryonic-like structures in vitro“.

Using laboratory chemicals, they demonstrated that specific protein kinase C isoenzymes play an essential role in the formation of the blastoid cavity, providing an easily accessible, scalable, versatile and disruptive alternative to blastocysts to study the early human development., Understanding early pregnancy loss and more about early developmental defects. In addition, pointed out that human pluripotent stem cells (CEP) which are derived from embryos before implantation or which are obtained by cell reprogramming, provide a valuable in vitro model for the study of early human development, and they hold great promise for regenerative medicine.

Recent advances in stem cell-based embryo models have opened up new possibilities for research using human stem cells. Although several structures have been generated that mimic specific aspects of early human postimplantation development, no model is available that summarizes the embryogenic events of the human blastocyst. “This work adds to the ‘in vitro toolbox’ that scientists can now use to study the more unknown stages of human pregnancy,” between weeks 2 and 4, where women would not normally know if they are pregnantSaid Teresa Rayón, specialist at the Francis Crick Institute.

Plasticity of virgin human embryonic stem cells

Recent studies have shown that naive embryonic stem cells are competent for differentiation into embryonic (epiblast) and extra-embryonic (trophectoderm and hypoblast) lines. “The ability of naive human embryonic stem cells WIBR3 to differentiate into cells that resemble all types of cells in a blastocyst has led us to test whether they can generate structures that mimic human blastocysts in vitro,” the researchers said. experts.

In summary, by taking advantage of the embryonic and extraembryonic bipotency of human CEPs, we have developed a strategy that allows the generation of human blastocyst-like structures through sequential lineage differentiation and self-organization. Human blastoids resemble human blastocysts in morphology, cell line composition and assignment, and transcriptional status.

Nevertheless, human blastoids provide a valuable model for basic and translational research as an accessible alternative to human blastocysts. Blastoid generation is evolutionary and lends itself to well-controlled disturbance experiences, and will offer a unique model to study human embryogenesis, early developmental defects, early miscarriages and new contraceptives.

Study of skin embryos

Another scientific study that developed a similar model of a human embryo from skin cells was created by an international team of scientists led by Monash University in Melbourne, Australia.

In a discovery that will revolutionize research into the causes of early miscarriages, infertility and the study of early human development, The team, led by Professor José Polo, successfully reprogrammed these fibroblasts or skin cells into a three-dimensional cellular structure that is morphologically and molecularly similar to human blastocysts, called iBlastoids, which can be used to early model the biology of human embryos. in laboratory.

The research, published today (to be confirmed) in Nature, was led by Professor Polo, of the Biomedicine Discovery Institute at Monash University and the Australian Institute of Regenerative Medicine, and includes the original authors, Dr Xiaodong (Ethan) Liu and doctoral student Jia Ping Tan too. such as 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 of UCLA in the United States.

This achievement is a significant advance for the future study of early human development and infertility. To date, the only way to study those early days has been to use rare and hard-to-obtain blastocysts obtained from IVF procedures. “iBlastoids will allow scientists to study the early stages of human development and some of the causes of infertility, birth defects and the impact of toxins and viruses on early embryos, without the use of human blastocysts and, more importantly, on an unprecedented scale. accelerate our understanding and the development of new therapies, ”said Professor Polo.

The Polo Lab successfully generated the iBlastoids using a technique called “nuclear reprogramming” which allowed them to change the cellular identity of human skin cells which, placed on a 3D “gelatin” scaffold called the extracellular matrix, organize themselves into a blastocyst. structures they called iBlastoids. IBlastoids models the general genetics and architecture of human blastocysts, including an internal cell mass-like structure made up of epiblast-like cells, surrounded by an outer layer of trophectoderm-like cells and a blastocoel-like cavity .

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