Hans Keirstead

Roman Reed is introducing Dr. Keirstead as the best stem cell scientist in the world.  “He’s like a brother to me.  He’s a pioneer.  He’s going to win the Nobel prize one day.  We’re lucky to have him here.”

Hans:  I’m going to go through a couple of the things I’ve developed with my teams.

(Background . . . Keirstead’s lab famously was first to coax embryonic human stem cells into differentiating into the exact kind of neural cell he wanted, which was oligodendrocyte precursors (OPCs).  He tested those pure OPC cells in both acute and chronic animal models, and in the acutes ONLY, was able to show that the OPCs did their job, which is to remyelinate naked axons.  The company Geron took that work to the FDA and asked permission to do human acute trials . . . which were then delayed for years.  The trials finally did start, but then Geron backed out.)

Hans: Geron . . . we had developed highly pure oligodendrocytes and gave 5 patients 1/10th of what we thought would be an effective dose.  The regulatory bar was extremely high, and there was a very long patient followup — 15 years before release to the public.  All of it worked, which is great, but the company was burning a LOT of money for what would be a small market size.  It’s on hold for financial reasons.

I’ve been intimately involved in the analysis and it’s my belief that the program will be resurrected.

(More background . . . he then goes on to talk about the status of his human motor neuron trials, which he has been working for years to see happen in the USA with Spinal Muscular Atrophy (SMA) babies, who suffer from a terminal congenital condition that mimics in some ways the loss of motor function people with SCI have.  He’s told us in the past that it would be faster to try this therapy with SMA than with SCI because there’s much more urgency in the former.)

The high purity human motor neurons for sc disease was placed on clinical hold at the FDA.  We went to the UK with it  . . . using these cells, we’ve established a long body of evidence that it works to restore all kinds of motor function.  We expect to see it go into trial in 2013.

(So apparently the US FDA didn’t go for the idea, but its counterpart in the UK did . . . )

Hans moves on from updates on old work to new stuff . . . we have made high purity human neuronal progenitors for SCI — these cells don’t make anything but neurons — no astrocytes, no oligodendrocytes.

What I decided to do is manipulate the pten gene.  We looked at a couple of pten inhibitors. If we block pten, we get bigger, faster, better, longer axon growth — a 40-50% increase in growth.  Neurons grow, and pten-inhibited ones grow much better.  You also get a lot more secondary neurite growth.

Pten inhibition promotes outgrowth beyond cAMP levels . . we know exactly how that works, i.e., which pathway is being employed.

But, you can’t add pten to people . . .what we can do is add it to cells in a dish and then add the cells to people.  It’s a temporary thing, which is good.  You don’t want it in you for a long time.

In animal models, we’re looking at double the outgrowth in vivo.

pten is big all over the regenerative medicine world . . . many labs exploring what it means to have found a gene that controls whether or not a neuron can regenerate.

Another major effort is to reprogram the astroglial scar.  This is different from development, which is a process of differentiation.  Pluripotent reprogamming is a process of doing that in reverse, and lineage reprogramming is turning one cell into another kind altogether.

What this means is taking astroglial cells from an SCI scar and turning back the clock so that they become like they were when they were young.  In their aged, scar phase they’re inhibitors — but in their young phase they’re  promoters of growth.

They started by establishing astrocyte cultures.  Then they chose some outcome measures, which in itself took a lot of doing. (He’s saying they needed reliable ways to know if they’d succeeded in turning back the clock.)  They landed on markers of proliferation, and what happens when ROCK is added to them, and laminin expression, and dorsal root ganglion neurite outgrowth, and migration — all of which show clear differences between old and young.

They treat their old astrocytes with factors that make them think they’re young, look young, act young.  The factors work.

This is evidence that they’ve succeeded — in a dish — in the goal of taking astroglial scars backwards and turning them from regeneration blockers to regenerations supporters.

(Next would be taking those newly rejuvenated astrocytes and seeing what happens when they’re given to animals with SCI.)

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2 Comments on “Hans Keirstead”

  1. […]  Getting an update from Dr. Hans Keirstead, who has taken “old” astrocyte cells from an SCI scar and turned back the clock — […]

  2. […] Dr.Hans Keirstead presentation at Working 2 Walk Conference November 02, […]

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