03 August 2010

Prof. Alain Privat: "Reconstructing the neuronal circuitry of a damaged spine looks like a much closer goal now"

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Prof. Alain Privat, Research Director at the French National Institute of Health and Medical Research (INSERM) and his team were the first to demonstrate the presence of stem cells in adult human spinal cords

During the European-funded RESCUE project they also proved that, by cultivating these cells in vitro, they can give not just neuron themselves, but also vitally important glial cells such as oligodendrocytes and astrocytes, which provide nourishment and help to control neuronal activity. These cells could play a key role in the reconstruction of the spinal cord and allow patients to regain mobility one day.

Which have been the goals of your research activities after the demonstration of the presence of stem cells in human spinal cords?
In order to try to do something for the patients, one of our first goals was to see where stem cells were present in the spinal cord of adult humans. Stem cells are able both to reproduce themselves and to transform into mature cells of the spinal cord, i.e. neurons and other cells. The demonstration of their presence in human spinal cords could give us the possibility to cure some of the lesions. If the cells are here, we know that if we take them out of the cord, if we cultivate them, we can transform them into neurons, so we need to find the tools in order to transform them inside the cord.

How is it possible to reconstruct the damaged spinal cord through stem cells?
One thing which is important to know when dealing with repair of the spinal cord, is that we don’t need to reconstruct completely the cord in order to have it work. We know that, and this is taken from works which have been done mainly in primates, that only 10% of the fibers, 10%, one of a ten, which is regenerated is enough to start to permit walking, control of the bladder, etc. So we don’t need to have a massive re-growth and a total reconstruction, but a few fibers, which find their way to their proper targets.
We could use these cells to repair the spinal cord in two ways: one would be to help the cells of the spinal cord to regenerate and the other to replace the cells which have been destroyed. These stem cells can do both.

Have you been able to prove the effectiveness of stem cells implantation to repair the spinal cord?
INSERM’s scientists cultivated these stem cells in test tubes and showed that they are capable of developing into all the different kinds of cell needed for the spinal cord to function properly. Once they had been grown, the scientists implanted stem cells into rats. They were able to follow their effectiveness at healing lesions on the spinal cord. Thanks to injections of stem cells, 80% of paralyzed rats regained some of their motor functions. What works on animals could, in the long term, work on humans. This would be either by injecting stem cells, or using genetic therapy to reactivate the stem cells already present so that they produce new neurons. The researchers were able to detect stem cells in spinal cord tissue thanks to the high quality tissue samples made possible by the collaboration between INSERM, Montpellier University Hospital and the French national biomedicine agency.

Which has been the most striking achievement of your experiments?
For the first time we managed to have all the series of experiments working from the beginning i.e. the harvesting of the cell, the transformation with genetic tools, the grafting, the survival of the animals, etc. This was the real time where we could see human stem cells injected into mice, for the first time transforming into neurons. It was very impressive and it finally worked. This means that we have found the right combination.

Considering the diversity of animals’ cells, when would you expect a future therapeutic use on humans?
These spinal cords came from animals that progressively regained some of their motor functions after injections of stem cells. The diversity of these cells and the way that they differentiate are still to be understood. Scientists are remaining cautious about future therapeutic uses of this breakthrough on humans. We are confident that at the best we will improve some of the patients’ capacities, but this won’t happen tomorrow, it will take time.



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