Stem cell treatment of spinal cord injuries

I have to admit that my first response to these reports out of Britain that stem cells had been successfully used to repair a complete spinal cord transection was skepticism -- incredulity even. They're reporting that a man with a completely severed spinal cord at level T10-T11 is able to walk again! The Guardian gushes! The Daily Mail gets in the act (always a bad sign)! When I read that the patient had an 8mm gap in his spinal cord that had been filling up with scar tissue for the last two years, I was even more doubtful: under the best of conditions, it was unlikely that you'd get substantial connectivity across that distance.

So I read the paper. I'm less skeptical now, for a couple of reasons. They actually did this experiment on 3 people, and all showed degrees of improvement, although the newspapers are all focusing on just the one who had the greatest change. The gradual changes are all documented thoroughly and believably. And, sad to say, the improvements in the man's motor and sensory ability are more limited and more realistic than most of the accounts would have you think.

The story is actually in accord with what we've seen in stem cell repair of spinal cord injury in rats and mice.

Overall, they found that stem cell treatment results in an average improvement of about 25% over the post-injury performance in both sensory and motor outcomes, though the results can vary widely between animals. For sensory outcomes the degree of improvement tended to increase with the number of cells introduced – scientists are often reassured by this sort of “dose response”, as it suggests a real underlying biologically plausible effect. So the good news is that stem cell therapy does indeed seem to confer a statistically significant improvement over the residual ability of the animals both to move and feel things beyond the spinal injury site.

Significant but far from complete improvement is exactly what we'd expect, and that improvement is a very, very good thing. It is an accomplishment to translate animal studies into getting measurable clinical improvements in people.

The basic procedure is straightforward. There is a population of neural cells in humans that do actively and continuously regenerate: the cells of the olfactory bulb. So what they did is remove one of the patient's own olfactory bulbs, dissociate it into a soup of isolated cells, and inject them into locations above and below the injury. They also bridged the gap with strips of nerve tissue harvested from the patient's leg. The idea is that the proliferating cells and the nerves would provide a nerve growth-friendly environment and build substrate bridges that would stimulate the damaged cells and provide a path for regrowth.

Big bonus: this was an autologous transplant (from the patient's own tissues), so there was no worry about immune system rejection. There were legitimate worries about inflammation, doing further damage to the spinal cord, and provoking greater degeneration, and part of the purpose of this work was to assess the safety of the procedure. There were no complications.

Also, I'm sure you were worried about this, but the lost olfactory cells also regenerated and the patients completely recovered their sense of smell.

Now here's the clinical assessment. Three patients were operated on; T1 is the one who has made all the news with the most remarkable improvement. There were also three control patients who showed no improvement over the same period.

Neurological function improved in all three transplant recipients (T1, T2, T3) during the first year postsurgery. This included a decrease of muscle spasticity (T1, T2) as well as improvement of sensory (T1, T2, T3) and motor function (T1, T2, T3) below the level of spinal cord injury.

A marked decrease of muscle spasticity of the lower extremities was observed in Patients T1 and T2 from the first day postsurgery and remained unchanged throughout the next 12 months. In Patient T1, the mean Ashworth score decreased from 1.25 to 0, and in Patient T2, from 3.25 to 1.12. Spasticity in lower limbs did not change essentially in Patient T3. Mean Ashworth score increased from 2.0 to 2.5. In contrast, there was no change of the Ashworth grade in patients from the control group after 12 months of rehabilitation.

The Ashworth scale measures the rigidity of the muscles -- a zero is normal tonicity, while a high score of 4 means the limb is rigid and resistant. That two of the patients showed a marked decrease in score is good news.

In Patient T1, the first symptoms of recovery of sensation below level of injury were noted at 6 months post- surgery. The patient reported tingling in the dermatomes S4–S5. This impaired sensation turned to a sensation of light touch or pin prick by 8 months post-cell grafting. In the same period, the patient gained voluntary adduction of lower extremities (2 points in the Medical Research Council Scale, MRC), and at 12 months, a slight voluntary flexion of the right hip (MRC 1), indicating conversion of the ASIA grade from A to C.

Patient T2 showed also symptoms of recovery of sensation in dermatomes S4–S5 at 9 months postsurgery. We also noted an increase in the strength of abdominal muscles in this patient, but as this type of motor function is not included in the ASIA score, we classified him as ASIA B.

After an initial decrease of the sensation concerning mainly the sensory level and the zone of partial preservation on the right, noted in the first 3 months after surgery, Patient T3 recovered sensation at 4 months to the state before surgery. In addition, new areas of sensation covering the dermatomes from T9 to T11 on the right side were noted 12 months after cell transplantation, and a slight increase in the strength of abdominal muscles was observed in the period from 4 to 12 months. As this type of neurological improvement is not scored in the ASIA classification, this patient was assessed as ASIA A.

The ASIA scale is a measure of the loss of motor and sensory function. An A is bad; it means there is no sensory/motor ability below the lesion site. A B means some sensation is retained, but there is no motor activity. A C means you've also got partial recovery of some muscle activity. A D (none of the patients reached this level) means that more than half the muscles are responsive. An E is normal function.

So the end result is that one patient upgraded all the way to C, another made it to B, and the third patient showed no significant recovery, although there were hints of some restoration of activity.

I think there's good reason to be optimistic and see some hope for an effective treatment for serious spinal cord injuries, but right now it has to be a realistic hope -- progress has been made. A cure does not exist.

But that's still some pretty good news.

Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, Huber J, Szarek D, Okurowski S, Szewczyk P, Gorski A, Raisman G. (2013) Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant. 22(9):1591-612.