Megan
Munsie, The
University of Melbourne and Helen
Abud, Monash
University
Researchers have
successfully grown model versions of early human embryos by
reprogramming cells from human skin. The breakthrough
potentially opens up new ways to study the earliest phases
of human development, learn more about developmental
disorders, infertility and genetic diseases, and perhaps
even improve the success of IVF treatment.
In a
study published
in Nature today, a team led by our colleague Jose Polo
discovered that when skin cells are treated in a particular
way, 3D structures similar to early human embryos form. A US-Chinese
research group led by Jun Wu also reported a similar
feat, creating structures that resemble a very early stage
of the embryo called a blastocyst.
While
this is an exciting scientific advance, it will also be
vital to consider the ethics behind this and other emerging
approaches to modelling human development.
Growing
human organs in a dish
Over the past 50
years, research has revealed a lot about how the different
organs of our bodies are formed, and what happens at a
cellular level during disease and illness.
Many of
these insights came from recent breakthroughs in stem cell
research, in which scientists can effectively create 3D
models, or miniature organs from human tissue, that resemble
the structure and function of particular organs in the
body.
These structures, known as organoids, have
been used to understand how
kidneys form, learn what happens to the developing brain
during
a Zika infection, and to test an array of therapies to
find the best ways to halt
the progression of bowel or pancreatic
cancers.
These advances rely on the innate
ability of stem cells to organise themselves into
characteristic anatomical and functional features when given
the right conditions. Researchers can use stem cells taken
from a patients own tissue to create 3D models of the
organ from which those cells were taken. Many, but not all,
organs have their own
specific stem cells.
Other approaches use a
more basic type of stem cell, called pluripotent stem
cells, obtained from human embryos or created in the lab
from a skin or blood cell through a process called
reprogramming. This approach means researchers can create
stem cells then coax them to mimic how a particular organ
forms. While these 3D structures are often referred to as
mini-organs, they usually only replicate certain
aspects of the organs architecture and
function.
Exploring the developmental black
box
While stem cells can reveal much about how
organs form, research so far has provided little insight
into the complex interplay between the developing embryo and
the lining of the womb required to establish and maintain a
pregnancy.
This period, covering the first few
weeks after implantation, is sometimes referred to as the
black box of development, as it is extremely difficult
to access reproductive material at this early stage.
Whats more, even in countries that allow
research on donated IVF embryos, studies are usually limited
to just the first
14 days after fertilisation, and alternative animal
models are of little value in revealing the unique process
of human embryo implantation.
Read more:Destroying
research embryos within 14 days limits chance of medical
breakthroughs
With miscarriages affecting
1 in 6 pregnancies, and high rates of infertility due to
failure of embryos to implant, we need better ways to
understand and address these devastating
outcomes.
Creating 3D models could provide
answers
Human pluripotent stem cells have been
used to create structures that replicate
specific aspects of development, but not the entire
embryo, at and immediately after implantation.
The
new discoveries reported today offer another way to explore
development around the time of implantation. Unlike
animal studies, in which the 3D model embryo is compiled
by assembling cells from pre-established stem cell lines,
this approach relied on adapting the technology used to
create induced pluripotent stem cells.
In the
approach taken by Polos group, skin cells from adult
donors were first treated to reprogram them over
several weeks, effectively resetting their development back
to an earlier, less specialised state.
The
researchers then grew these cells in 3D clusters for six
days, after which some of them formed structures very
similar to blastocysts the final stage of
embryonic development before implantation. These lab-grown
structures are dubbed iBlastoids.
Growth
process for human blastocysts (top) and iBlastoids grown in
the lab from human skin cells (bottom).Monash
Biomedicine Discovery Institute
The second
group cultured human pluripotent stem cell lines – both
embryonic stem cell lines and those created through
reprogramming – in a slightly different two-step process to
encourage 3D clusters to form. They called their structures
blastoids.
While iBlastoids and blastoids
both seem to be structurally and functionally similar to
real blastocysts, it is not yet clear exactly how closely
they resemble true embryos formed by a sperm and an egg.
While the models were shown to share gene patterns and
respond in culture in ways characteristic of actual embryos,
researchers also saw significant anomalies, such as
unsynchronised growth and cells that are not usually present
in an embryo.
Ethical issues
It can be
hard to decide where we should draw the ethical line between
using stem cells to grow model embryos, and research
on real human embryos created by IVF.
Some people
may see no ethical distinction between these two processes
at all. Others might support the creation of models but only
for specific types of research, such as to understand the
origins of infertility or genetic disease. Those people may
draw the line at attempts to use these models to test
gene-editing techniques to correct genetic diseases rather
than simply study them.
When considering these
ethical issues, we need to address three important
questions:

• what are the likely
  benefits?
• can the scientific goals be
  met by other means?
• what is the
  appropriate oversight process?

While
3D models are not human embryos, existing national laws
around the creation and use of IVF embryos may provide
useful guidance and oversight. Many countries have
specialised review committees to provide independent advice
to researchers and ensure ethical
transparency.
Above all, we need to approach this
issue carefully. The science is complex, and likely to
trigger many of the same concerns raised 25 years ago by
breakthroughs in cloning
technology. One thing seems clear, just as it was back
then: this new technology should only be used for laboratory
research. Any attempt to use it to establish pregnancies in
humans or animals must be strictly prohibited.
Read
more:Dolly
the Sheep and the human cloning debate – twenty years
later
The International
Society for Stem Cell Research will soon release a new set
of guidelines that are likely to provide more explicit
recommendations for research in human embryo modelling. As
it has done in the past for other ethically charged issues,
this global approach is essential. There is too much at
stake to ignore the complexities.
Megan
Munsie, Deputy Director – Centre for Stem Cell Systems
and Head of Engagements, Ethics & Policy Program, Stem Cells
Australia, The
University of Melbourne and Helen
Abud, Professor, Head of the Department of Anatomy and
Developmental Biology and Director of the Organoid Program,
Monash Biomedicine Discovery Institute, Monash
University
This article is
republished from The
Conversation under a Creative Commons license. Read the
original
article.
© Scoop Media