14. Development in a dish
Working with animals is difficult, to get approval from various committees, they are expensive, etc.
Many attempts to study development outside animals.
Many drugs don’t make it past the pre-clinical stage. So that means that lots of animals have been
used up until that point but
without anything to show as result
for further research in patients.
what are the alternatives? We
would like to reduce the first peak
of costs that are coming from
experiments on animals. As the
second peak of costs is after pre-
clinical stage where experiments
will be done on humans.
There are 3 main strategies possible:
Stem cells allow to create body parts without the full animal model. We can’t study on humans but
we can form body parts of human SC’s and do experiments on them.
- Embryonic stem cells = ESC
o Very efficient
o Ethical issues
- Tissue stem cells = TSC
- Induced pluripotent stem cells = iPSC
Embryonic Stem Cells = ESC
Started in the 60’s they were able to start colony formation. Then in 1981 came a similar paper where
they were able to establish a culture of pluripotent cells derived from mouse embryos. This was a
huge breakthrough in the entire strategy to clone/work/manipulate animals.
In 1998 the first human stem cell lines were developed derived from human blastocysts. This shows
that there is no limit to which organism we can contain in a stem cell form.
History
2001 major problem without
funding, research stopped! However
it also pushed for innovation.
Work with stem cells without
embryos.
,ESC come from the early blastocysts from the inner cell mass.
How do the properties of stem cells change with age know the terminology!
The first cell
lineage that will
disappear is the
germ line, that’s
the only thing
pluripotent sc’s
cannot form.
How do we characterize and define
stem cells?
- symmetric division: 2 daughter
cells identical to the mother
cell. So nothing changed 1 cell
became 2 with the exact same
properties!
- Self-renewal
, Once you pick your SC’s then you
would like to expand them in
order to manipulate them. To do
that you grow them on a plastic.
Better to grow the SC’s in space
Hanging drops
Cells hanging in the drops of
medium so they do not touch any
plastic. After a while you can
collect them to grow/differentiate
them.
Quality of SC colonies is classified by the edges of the colony, the sharper
the edges the better.
High quality
medium
quality low quality
What do you want to do with them and
what can you do with them?
artificial vs natural mouse embryo, no
way to tell the difference!
Also further in development
no way to see the difference between artificial and real embryo. Even in gene expression there is no
obvious difference!
We can make embryos without any animals!
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