Human embryo-like models created from stem cells to understand earliest
stages of human development

Date:
June 27, 2023
Source:
University of Cambridge
Summary:
Scientists have created a stem cell-derived model of the
human embryo in the lab by reprogramming human stem cells. The
breakthrough could help research into genetic disorders and in
understanding why and how pregnancies fail.


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FULL STORY ========================================================================== Cambridge scientists have created a stem cell-derived model of the human
embryo in the lab by reprogramming human stem cells. The breakthrough
could help research into genetic disorders and in understanding why and
how pregnancies fail.

Published today in the journal Nature, this embryo model is an organised
three- dimensional structure derived from pluripotent stem cells that
replicate some developmental processes that occur in early human embryos.

Use of such models allows experimental modelling of embryonic development during the second week of pregnancy. They can help researchers gain
basic knowledge of the developmental origins of organs and specialised
cells such as sperm and eggs, and facilitate understanding of early
pregnancy loss.

"Our human embryo-like model, created entirely from human stem cells,
gives us access to the developing structure at a stage that is normally
hidden from us due to the implantation of the tiny embryo into the
mother's womb," said Professor Magdalena Zernicka-Goetz in the University
of Cambridge's Department of Physiology, Development and Neuroscience,
who led the work.

She added: "This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will let
us test the function of specific factors, which is difficult to do in
the natural embryo." In natural human development, the second week
of development is an important time when the embryo implants into the
uterus. This is the time when many pregnancies are lost.

The new advance enables scientists to peer into the mysterious 'black
box' period of human development -- usually following implantation
of the embryo in the uterus -- to observe processes never directly
observed before.

Understanding these early developmental processes holds the potential
to reveal some of the causes of human birth defects and diseases, and
to develop tests for these in pregnant women.

Until now, the processes could only be observed in animal models, using
cells from zebrafish and mice, for example.

Legal restrictions in the UK currently prevent the culture of natural
human embryos in the lab beyond day 14 of development: this time limit was
set to correspond to the stage where the embryo can no longer form a twin.

Until now, scientists have only been able to study this period of human development using donated human embryos. This advance could reduce the
need for donated human embryos in research.

Zernicka-Goetz says the while these models can mimic aspects of the
development of human embryos, they cannot and will not develop to the equivalent of postnatal stage humans.

Over the past decade, Zernicka-Goetz's group in Cambridge has been
studying the earliest stages of pregnancy, in order to understand why
some pregnancies fail and some succeed.

In 2021 and then in 2022 her team announced in Developmental Cell, Nature
and Cell Stem Cell journals that they had finally created model embryos
from mouse stem cells that can develop to form a brain-like structure,
a beating heart, and the foundations of all other organs of the body.

The new models derived from human stem cells do not have a brain or
beating heart, but they include cells that would typically go on to form
the embryo, placenta and yolk sac, and develop to form the precursors
of germ cells (that will form sperm and eggs).

Many pregnancies fail at the point when these three types of cells
orchestrate implantation into the uterus begin to send mechanical and
chemical signals to each other, which tell the embryo how to develop
properly.

There are clear regulations governing stem cell-based models of
human embryos and all researchers doing embryo modelling work must
first be approved by ethics committees. Journals require proof
of this ethics review before they accept scientific papers for
publication. Zernicka-Goetz's laboratory holds these approvals.

"It is against the law and FDA regulations to transfer any embryo-like
models into a woman for reproductive aims. These are highly manipulated
human cells and their attempted reproductive use would be extremely
dangerous," said Dr Insoo Hyun, Director of the Center for Life Sciences
and Public Learning at Boston's Museum of Science and a member of Harvard Medical School's Center for Bioethics.

Zernicka-Goetz also holds position at the California Institute of
Technology and is NOMIS Distinguished Scientist and Scholar Awardee.

The research was funded by the Wellcome Trust and Open Philanthropy.

* RELATED_TOPICS
o Health_&_Medicine
# Pregnancy_and_Childbirth # Stem_Cells # Birth_Defects
# Human_Biology # Lymphoma # Medical_Topics #
Prostate_Cancer # Skin_Cancer
* RELATED_TERMS
o Embryonic_stem_cell o Stem_cell o Adult_stem_cell
o Stem_cell_treatments o Somatic_cell o
Somatic_cell_nuclear_transfer o Gene_therapy o
Bone_marrow_transplant

========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
text of this story is licensed under a Creative_Commons_License. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Bailey A. T. Weatherbee, Carlos W. Gantner, Lisa K. Iwamoto-Stohl,
Riza
M. Daza, Nobuhiko Hamazaki, Jay Shendure, Magdalena
Zernicka-Goetz. A model of the post-implantation human embryo
derived from pluripotent stem cells. Nature, 2023; DOI:
10.1038/s41586-023-06368-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/06/230627123010.htm

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