Spinal Cord Restoration

Human stem cells helped monkeys recover from spinal cord injury

Daria Spasskaya, N+1

Scientists have achieved partial restoration of limb mobility in monkeys with spinal cord injury. In an article published in Nature Medicine, the authors explain that recovery was achieved by implanting human precursor cells of neurons into the site of injury. After the cells took root, the intensive growth of axons and the formation of new synapses began at the wound site, which caused the improvement of the motor functions of the animals. The next stage of the study should be experimental therapy of patients.

Complete recovery of the spinal cord after injury is considered almost impossible, since for this neurons need to regrow axons – long processes through which impulses are transmitted to other nerve cells. This process is hindered both by the absence of special growth factors – neurotrophins, and by the suppression of the growth of processes by the connective tissue extracellular matrix (scar tissue formed at the site of injury).

In modern medicine, there are cases when complex therapy, including, for example, electrical stimulation using implanted electrodes or training using a special neurointerface in combination with an exoskeleton, helped patients paralyzed after spinal cord injury to partially restore the sensitivity and mobility of the limbs and even stand on their own. However, the mechanism underlying these cases is unknown. Doctors suggest that patients have learned to use the remaining nerve fibers rather than grow new ones.

For the treatment of spinal cord injuries, scientists have previously proposed using stem cells. Indeed, it is easier to introduce new cells into the site of damage, which will develop into adult neurons with appendages, than to force "old" cells to regrow axons. Researchers and surgeons from the Department of Neuroscience at the University of California (USA) have long been developing a technology for restoring the spinal cord in rats using partially differentiated precursor cells of neurons, and have achieved some success. In a new paper, scientists presented the results of an experiment on monkeys, which can be considered preclinical tests before starting experimental therapy for humans.

The experiment involved nine adult male rhesus monkeys who had their spinal cord damaged in the cervical region. For two weeks, the animals recovered from the injury, and after that, 20 million stem cells were implanted into the injury site.

The nerve tissue progenitor cells used in the experiment were obtained from an eight-week-old human embryonic spinal cord and maintained in the laboratory as a cell line. In addition, the cells expressed a green fluorescent protein so that they could be conveniently monitored in the body of experimental animals. Implantation was accompanied by the addition of a cocktail of growth factors to the cells. Animals were injected with immune suppressing drugs after surgery to prevent the rejection of foreign cells.

In five of the nine animals, the cells took root and contributed to the tightening of the wound for several months. At this time, the researchers observed the expression of markers of cell differentiation into "adult" neurons and auxiliary cells of the neuroglia. Most importantly, a few months after implantation, axon growth and the formation of new synapses (contacts between neurons) with "host" neurons were observed at the site of injury. In total, the researchers observed hundreds of thousands of new appendages.

(a) – the scheme of the experiment. Blue indicates "host" neurons, green – implanted stem cells. New axons germinate under the influence of growth factors and form synapses and nerve chains. (b) and (c) – the place of damage before and after implantation. (d) – engrafted new cells expressing green fluorescent protein (Rosenzweig et al., Restorative effects of human neural stem cell grafts on the primate spinal cord).

The mobility of the macaques' limbs, disrupted by the injury, also partially recovered within a few months. The motor functions of the limbs were evaluated according to 25 criteria, and according to most of them, visible improvement was observed in those monkeys who had implanted cells, which continued over time. The researchers did not observe a complete recovery in any case, however, the authors note that the process of axon germination and the formation of connections and nerve chains takes a long time, and experimental animals were observed for a maximum of nine months.

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