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Posts Tagged ‘Stephen Davies’

Breakout Session 4: Dr. Davies and Dr. Simon Archibald

Posted by katewillette on April 13, 2008

The name of the talk is Decorin and GRP-derived astrocytes.  The video Bruce made of his talk last year is on youtube, for those who want to see part A.  I’ll go find a link if I can before I post this.  This is it: http://youtube.com/watch?v=QnBsnhzy1Ug

The glial scar is a physical and molecular barrier to axon growth — a fact that’s been known for a long time.  There’s an image up from a 1999 article in the Journal of Neuroscience that shows the green lines of axons straggling toward this thing that looks like a joint in a knee, where they stop dead. It’s the injury site.

His lab has been after 2 strategies:

Overcome scar and inhibitors to promote axon regeneration/plasticity.

Replace lost glia to bridge axon growth across the injury site.

What’s the right cell type for a bridge?

Non-CNS cell types (Schwann, engineered fibroblasts, olfactory ensheathing cells, macrophages, esc’s, marrow stromal cells) plus CNS cells, and 70% of adult CNS cells are astrocytes . . . but there are different kinds. Can we make the right kind?

Embryonic Stem Cells give rise to neuron prestricted precursors and glial restricted precursors (GRPs).  GRP’s can make either GDA Bmp or GDA gp130’s

The BMP’s have low inhibitor levels, they’re high in growth factors, and highly supportive of axon growth.  The gp130’s are the exact opposite.

So, where do you get grp cells?  From esc’s, unless you can genetically engineer the adult stem cell . . .a process that is not done yet.

So when you transplant the gdabmp’s what happens?  A ton of cells migrate into the margin of the injury and they align themselves very neatly — the opposite of what happens normally, where cells are all mixed up and helter skelter. They actually measured the misalignment between axons as about 59 degrees without the astrocyte gdabmp and 11 degrees with it.

These are the same slides we saw last year, and they still knock me out. All this was published in the Journal of Biology last year, after Dr. Davies was good enough to share it with us.  So what about functional recovery? The rats that got the good astrocytes are at almost full recovery — and the ones that got the bad ones get nada.

Neuropathic Pain . . . (sometimes called allodynia) can be made WORSE by implanting “naive” neural stem cells.  They turned into grp’s, then the bad kind of astrocytes, and pain was the result.  So they tested gdabmp, gdagp130, and grp’s — the rats that got the bmp’s were like normal rats, but the others were in serious pain–so serious that they had to stop the experiment ahead of time.

This is a major reason for people to hold off on the idea of getting any kind of undifferentiated stem cell injection to get recovery.  It’s not unlikely that the result will be more neuropathic pain.

Bottom line: the bmp astrocytes are all gain and no pain. I like that combination.

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