most complex life forms ever developed entirely in Petri dishes can
pump blood through tiny beating hearts, gradually growing nerves and
muscles in a laboratory.
These little collections of mammalian cells form rudimentary mouse embryos, built from scratch out of stem cells - cells that have the potential to develop into any other cell type in the body.
While scientists have successfully been creating synthetic organs called organoids for a while now, these lack the full variety of cell types found in the
real deal. This human-built mouse embryoid is a whole lot more
"Watching an embryo develop is a marvelous thing to behold," said developmental biologist Christine Thisse from the University of Virginia, one of the authors of the study.
is amazing is that we can get the variety of tissues that are present
in an authentic mouse embryo. [This] model shows that we are able to
induce cells to execute complex developmental programs in the right
succession of steps."
embryoid isn't a complete unborn mouse, and it can't fully develop into
one as key parts are still missing - like a giant chunk of the brain.
But the complexity of this experiment takes researchers a huge step
towards being able to build fully functional organs in a lab.
"Human organs are made of multiple cell types that originate from different parts of the growing embryo," said developmental
biologist Bernard Thisse. "The gut, for example, is made from cells
that form a hollow tube. Models of this tube in a dish have been made
and are called gut organoids.
this tube is not enough to make a functional gut because this organ
contains other components, such as smooth muscles, blood vessels and
nerves that control the function of the gut and which are made from
cells of different origins.
only way to have all the variety of cells necessary to the formation of
functional organs is to develop systems in which all precursor cells
are present. The embryo-like entities we have engineered using stem
cells are providing just this."
these fully functioning biological systems requires getting a slew of
things just right - such as the correct cell type, spatial location, and
timing of cell signals to get the desired outcome. Synthetically
recreating these complex processes is only possible thanks to
generations of research in developmental biology, including this team's previous research on zebrafish.
Many previous attempts have been built upon. These were missing things like entire types of tissues, didn't form a head structure, failed to organize tissues correctly, or develop to the embryonic stage called gastrulation.
of these issues involved the need to spatially confine the
developmental chemical signals within the forming embryoid. Thisse and
colleagues developed a way to do this in their zebrafish experiments -
creating centers for the signalling chemicals that provide the cell
clusters with a sense of direction - back and front, head and tail.
They could then control the timing, size, and strength of these signals.
work has now culminated in these miraculously functioning mouse
embryos, with all the normal early embryonic tissue layers. The
correctly organized cells and tissues are arranged properly around the
embryoid spinal cord precursor (the notochord), including developing
digestive, muscular, nervous and circulatory systems and a beating
the embryoid is still missing parts of the brain, and the team suspects
this may be because the chemical signal telling the cells they're at
the butt end (called a WNT morphogen) spread too far.
the techniques we have developed, we should be able, at some point, to
manipulate molecular signals that control embryo formation, and this
should lead to generating embryo-like entities containing all tissues
and organs including the anterior brain," said Bernard Thisse.
researchers hope to learn how to fully control and manipulate the
embryoid development, and think it may become a powerful tool for
all the variety of tissues made allows us to hope that the scientific
community will be able to build organs with a proper vascularization,
innervation and interactions with other tissues," Christine Thisse said.
is essential to be able one day to produce functional human replacement
organs in a dish. This would overcome the shortage of organs for
Their research was published in Nature Communications.