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Stem cells to promote nerve regeneration

Interview with Professor Tuszynski

Mark Tuszynski is a professor of neurosciences and founding director of the Translational Neuroscience Institute at the University of California – San Diego.

We caught up with him to learn about his background and research into the use of stem cells to treat spinal cord injury.

Did you always want to be a scientist?

I don’t know if I consciously decided to pursue it, but I was always interested in medicine.

I read a lot of science fiction as a child. The book ‘Flowers for Algernon’ had a considerable impact on me – it is a story of a mentally disabled man who has his intellect restored through the use of science. In a way, some of the work we’re doing was probably somewhat inspired by that.

When I was in high school I wondered why there’s not an effort to repair the injured spinal cord using cell transplantation (placing healthy cells in the injured area). During a rotation in medical school, I worked on spinal cord injury (SCI) research and found research was already taking place in this field.

How did you progress into your current position?

Following medical training as a neurologist, I went full time into the lab where I obtained my position after completing my PhD in neuroscience at UCSD in 1991. I’ve been here since then.

Can you tell us simply about your area of research?

Our lab is focused on spinal cord injury and neurodegeneration (when nerve cells in the brain or spinal cord stop working or die).

Cells in the spinal cord fail to regenerate for a few reasons: 1) following an injury, a cavity remains filled with fluid and fibrous tissue which is inhospitable for a nerve to attach and grow through; 2) a lack of ‘growth factors’ (growth promoting chemicals); 3) presence of chemicals inhibiting growth.

For many years it was believed that an injured adult nerve cell couldn’t regrow. However research has shown these cells revert to an early regenerative state for 2 weeks following the injury. This can be amplified to make them regenerate even more.

Key Terms

  • Stem cells: Cells with the ability to become other cells in the body.Some stem cells, such as multi-potent stem cells are limited in what they can become. Others, like pluripotent stem cells can become any cell in the body
  • Axons: the long projection of neurons (nerve cells). Electrical signals transmit along axons, which connect or ‘synapse’ with other neurons and allows them to communicate.

    The longest axon in the body is that of the sciatic nerve, which is over a metre long and travels from the lower back down to the foot.

Does length of time after injury affect the outcome of the research?

If we put stem cells into acute (early) injury it results in hundreds of thousands of axons and host axons regenerating into the stem cells.

If we delay that for 6 months, we see roughly half as much growth – something has changed in the chronic injury and we are actively studying why this is different.

Humans who are chronically injured for over ten years tend to lose about half of the axons originally present at the time of the injury – however, there are still axons remaining. In theory, those axons could be recruited to regenerate.

What is the current state of play regarding research progress?

There are a million axons in the spinal cord. Thirty years ago, it used to be exciting to get 100 axons to grow one millimetre beyond the lesion in experiments.

Now, using stem cell grafts, we see roughly 300,000 axons growing 50 mm in monkeys.

Some labs implant stem cells above and below the injury site to myelinate the axons (the process of regenerating the fatty coating around nerve axons to improve signalling).

In our lab, we implant the stem cells in the site of injury itself because the vast majority of function lost following injury is due to the cut axons.

We hypothesise that the injured axons will then regenerate into the injury site and form synapses (connections) with the stem cells, which in turn will form synapses with the injured axons below. So far, the evidence absolutely supports this hypothesis.

Read more about how stem cells are used in research in our latest Connections magazine

Do we know when any meaningful therapies may be available?

It’s different for acute and chronic injuries. We’re aiming to start clinical trials for acute injury in 2 years – chronic injury will follow that but we cannot put a timeframe on it yet.

Lastly, what motivates you?

As a physician, one can touch the lives of thousands over the course of a career, but as a scientist one can touch the lives of millions by developing a useful therapy for human disease. That’s the inspiring motivation to do the work we’re doing.

It’s a real honour and privilege to be in a position to do the science and bring it to people. My only hope is that we have an impact.

Professor Tuszynski's latest study

Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury, Tuszynski et al., 2022