Science Time: First-in-man Clinical Trials on Directly Re-programmed Autologous Neural Stem Cells

Oh, joy, Barry Long is going to emcee the rest of the day. He’s up there now talking about his injury . . . motorcycle crash. He just described himself as one of those “super-gimps” who bungie jumps, skydives, all that. And he does motivational speaking all over the country. Describing his 10 yr old daughter telling him recently at a family wedding that she wishes he could walk her down the aisle . . . and that’s why they’re here. Because some of the people who are going to make that possible are in the room. (applause, amen)

The speaker is going to be Jan-Eric Ahlfors of New World Laboratories, Inc.

He takes the stage.

15 yrs ago I never thought I’d end up here . . . but one summer I got an internship at a local hospital to work with patients, and I chose neurology. I got to see all kinds of patients & that sort of changed things. I felt like many of the doctors had lost their emotion toward th patients. After seeing them, we’d talk aftwerwards about what they thought, and it seemed that their emotion was buried.

I got to see new patients, and patients with older injuries — and after that I started to look harder at research. And I got into a very special lab run by one of the forefathers of tissue engineering. That was really my first strong lab experience, where I learned how to do things differently. I was an undergrad among PhDs and postdocs, but was treated as one of the team.

Their attitude was that it might be interesting to take a naive kid and put him in a lab before he got indoctrinated with the idea that nothing could be done.

So he started looking at nature itself, with its 3 billion years of Research and Development. The lizard, for example, can regenerate just about everything. These animals regrow their limbs, spinal cord, eyes, whatever. (Slide is an image of an axolotl salamander, called the “master of regeneration.”)

How does it regrow a leg, for crying out loud? That seems impossible.

But he says that what we need starts with a biomatrix — a regeneration matrix. It needs to directly reprogram the needed tissue-specific cells to start the process. His team has actually produced this thing for humans. Regeneration Matrix is a trademarked term. And they’ve shown in the lab that human neuroprogenitors proliferate, differentiate and extend neurites when in contact with that stuff.

Say what? Neuroprogenitors means this: cells that are like the basic stuff from which the kinds of cells you find in a healthy spinal cord arise. So this is good news. In a transected rat cord, what you get with the matrix placed into the cavity is regrowth of spinal cord tissue.

In pigs, this stuff recruits oligodendrocyte precursors to the site of the injury. In human language, that means it acts like a siren to the cells that provide the wrapping/insulation to axons. And in their rat model over 4 weeks you see the rats recovering function as measured on the good old BBB model.

On the walking beam test, they end up about halfway between untreated animals and uninjured animals. They’re like ASIA D guys.

Overview. They’ve seen sensory and motor regeneration in pigs and in 3 tested spinal cord injury models in rats (contusion, resection, hemisection). When they look at what’s going on in dishes, they see

  • a 10-fold increase in neuronal and astrocyte differentiation
  • a 2-fold increase in neurites and neurite length
  • and no tumor growth.

Yikes. He’s got a slide up with about 50 tiny little images meant to show that the word “stem cell” is a generic term, like “drug.” Yes. There are lots and lots of kinds, each of which can only do one thing.

What we want is neural stem cells. That specific kind. Where do you get them? Well, that’s a problem. You don’t have any extra ones lying around in your body. So about 10 years ago they started trying to replicate what salamanders do. Axolotl is able to REPROGRAM its own cells right at the injury site to become the kind of stem cells it needs.

Okay. Remember Dolly the Sheep? She was cloned by taking a cell from the body of the original sheep, putting it into an egg, fertilizing that egg, and growing it into a sheep.

We don’t want to clone ourselves . . . we just want some neural stem cells. So what they did is directly reprogram neural stem cells. They’ve been able to make them out of blood cells, skin cells . . . whoa. And they spontaneously regenerate as neurons. They “work” in the sense that they express all the right proteins, just like regular neurons. They also by themselves spontaneously form myelin, the “insulation” we need for messages to travel between neurons.  They can form synapses.

New slide title: Human directly reprogrammed neural stem cells work better in a broken rat cord than human fetal neuroprogenitor cells — the fetal cells are at the moment considered the “gold standard” for regeneration.

They’re much safer in terms of tumor risk, too.

They’ve been tested by the Canadian National Research Council.

They’re looking now at differentiating their cells into specific lineage. (meaning,

This is technology developed over 15 yrs by 100 researchers. It’s proven in animal studies. There’s evidence of functional recovery in humans with chronic sci. This technology can be extended to other cns diseases. They’re your own cells so it’s ethical. We’re still in early stages; there’s much more work to be done.

BUT people — this is a new thing. And it’s promising as hell.

Q: What about bladder function?

A: What we’ve seen is that it doesn’t matter what your injury level is. Once you get regeneration, things begin to work.

Q: Were your animals all acute?

A: No. We couldn’t get approval to work on severe chronic models. We’re trying to work out a way to test in a different CNS issue.

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