
Drug Combo Creates New Neurons from Neighboring Cells - lettergram
https://www.technologynetworks.com/neuroscience/news/drug-combo-creates-new-neurons-from-neighboring-cells-315118
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lettergram
Even though I shared this - I’d like to add I’m having trouble believing it.
I’d really like to see replication on this one.

Although it’s possible to change cells, once a cell has taken a form, it’s
used resources. Having a cell shift to a new form seems nuts.

It may be possible, but I’m dubious. I find it more likely that their
experiment(s) were contaminated, which seems relatively easy to do in this
case.

Anyone with more experience have any thoughts?

I minored in bioengineering, but that was years ago, so I have limited
knowledge.

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dekhn
Welcome to the modern era of induced pluripotent stem cells. 2012 Nobel Prize
With just a little cocktail, usually of transcription factors, you can make
one type of cell turn into another. usually, you will convert it to a less
differentiated (cells are created in a sort of tree structure where the leaves
are more and more specialized) form, which can then be pushed to develop into
other specialized forms.

This is really common in the lab now. You can use them to create organoids
which are like mini-organs that have a lot of the properties of, say, a lung
or a liver or a stomach or a brain, but aren't a full organism. Very useful
for making models of mammalian biology.

By the way the discovery that led to this was a huge surprise (at least, that
so few factors were required to transform cells) but there is still very
little known, IE we can't arbitrarily convert one cell type to another
reliably. Culturing mammalian cells is pretty hard.

~~~
Zenst
So would it be possible using this approach of cell transforming to target
cancer cells?

~~~
echelon
Targeting cancer cells is hard. One of the functions of the immune system is
to clear out pre-cancerous disease and error state. Cancer proliferates
_because_ it evolves in situ to evade immune regulatory checks.

One of the reasons stem cell technology is moving so slowly is that, apart
from mammalian cell culture being hard, we're extremely anxious about messing
with the growth pathways. Tripping up the gene expression is what causes
cancer in the first place. We're trying to find exploits in the same machinery
to induce novel transformations without kicking the cell into unregulated
growth. It's going to be a long time before I let something like that into my
body.

~~~
incongruity
You make a bunch of solid points, IMHO, but to your last sentence - If I’m
facing dying due to a neurodegenerative disease, I’d be willing to roll the
dice on the possibility of cancer. Facing death seems like a powerful
disinhibitiory driver to me....

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twic
From the paper:

 _After spending several years using various methods to deliver small
molecules in the mouse brain in vivo, we have not achieved definitive success
of chemical conversion inside mouse brains despite the observation of a few
neurons after chemical treatment. This is rather disappointing, but we are
still continuously trying direct in vivo chemical conversion in the mouse
brain. The biggest challenge for in vivo chemical conversion is how to
maintain a constant concentration of small molecules inside the brain without
causing a severe invasive damage to the brain. We have tried using biomaterial
to encapsulate small molecules, but, perhaps because our small molecules are
too small or we have not found the right biomaterial for such small molecules,
the small molecules we applied might not stay for a long time inside the
brain. We also tried an osmotic minipump (Alzet) but the tip of the insertion
caused significant tissue damage inside the brain, and the injury induced many
DCX+ cells that were mainly reactive astrocytes 2 weeks after drug treatment
(Figures S7I–S7K)._

Shame, but this is an entirely understandable problem, and these are still
early days!

 _On the other hand, during our vigorous testing of in vivo chemical
reprogramming, we accidentally found that core drugs significantly increased
adult neurogenesis in the mouse hippocampus (Figure 7). We initially injected
core drugs through intracranial injection into the hippocampus and sacrificed
the mice 7 days later (Figure 7A). We observed remarkable increase of DCX-
labeled newborn neurons together with Ki67-labeled proliferative cells in the
dentate granule layer (Figures 7B–7E)._

So, not conversion of glia into neurons, but production of new neurons from
progenitor cells. That's still really useful! The hippocampus is what gets
whacked in a load of different brain disorders (wikipedia tells me Alzheimer's
and other dementias, PTSD, schizophrenia, and depression, for starters), so
being able to drive neurogenesis there sounds really useful.

~~~
buboard
its still debatable however if there is neurogenesis in the human hippocampus
so not sure if this method results are transferable. it would be cool if it
worked generally though. alzheimer's causes neuronal loss throughout the
cortex, while parkinson's mostly on dopaminergic neurons.

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vgoh1
So the paper describes a way to make new neurons. Any indication that adding
new neurons will actually improve cognitive abilities? I know nothing about
neuroscience, but I could see a scenario where it is analogous to adding a
computer to a computer room, with nothing on the hard drive, and no network
connection.

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daenz
If it's anything like an artificial neural network, adding new neurons or new
neuron connections likely causes degradation in the overall abilities of the
NN. Having neurons and connections is important, but the connections
themselves have to be learned, selected, pruned to have overall value to the
system.

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gotocake
The original and open paper is a good read: [https://www.cell.com/stem-cell-
reports/fulltext/S2213-6711(1...](https://www.cell.com/stem-cell-
reports/fulltext/S2213-6711\(19\)30004-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671119300049%3Fshowall%3Dtrue)

Obligatory “in a Petri dish” codicil.

Obligatory xkcd: [https://xkcd.com/1217/](https://xkcd.com/1217/)

