Artificial neurons repair spinal cord damage

Researchers studied a specific type of cell: spinal interneurons V2a, which act as connecting elements in neural circuits and are involved in controlling movement and breathing. Now, scientists have learned how to obtain these cells from stem cells and transplant them into damaged spinal cord. A key achievement was that transplanted human V2a interneurons not only survived in the injury zone in rats but also formed new connections with the animals’ own neural circuits, improving motor function related to breathing.

The development of the method took about a year and a half of trial and error. The team led by Lana Zholudeva improved the differentiation protocols to obtain the specific subtypes of neurons from human stem cells. An important practical step was to ensure the possibility of freezing the obtained cells in test tubes and then thawing them for use; this step is critically important for the future clinical translation of the therapy.

The experiment was conducted on adult rats. The cells were transplanted a week after the injury to the cervical spinal cord; it is precisely these types of injuries that most commonly occur in humans and lead to impaired respiratory functions. Two months after the transplantation, it was recorded that the new cells not only survived in the aggressive environment of the damaged area but also formed functional connections with the surrounding neurons. When the transplant site was stimulated, an increase in diaphragm activity was observed. Furthermore, when researchers activated the rats’ own neurons in the brainstem (which run from the brain to the spinal cord), the transplanted cells responded — this confirmed their integration into the existing neural network.

Under normal conditions, differences in breathing between the animal groups were not very noticeable. However, under functional stress, for example, in conditions of reduced oxygen content or increased carbon dioxide levels, when the diaphragm has to work harder, the pattern became more obvious. Most of the injured rats without transplantation showed signs of respiratory failure. At the same time, three‑quarters of the animals that received V2a interneurons successfully coped with the load. According to Zholudeva, this reflects the difference between a patient who, due to a common cold, may end up back on a ventilator, and a patient who retains sufficient functional reserve to cope with such stress.

A subgroup of transplanted V2a neurons was also identified, which were most likely to integrate into the host’s respiratory circuits and contribute to recovery. Further work will be aimed at increasing the predictability and effectiveness of such integration.

Before moving on to clinical trials in humans, a number of tasks need to be addressed. First, to test the effectiveness of the approach on larger animals. Second, to determine whether the therapy will be equally effective if it is applied not a week after the injury, but months or even years later. In addition, the team plans to expand the approach to other functional circuits, in particular those that control the movements of the arms and hands. For patients with a cervical spine injury, restoring these functions is often the top priority.