An international team of scientists has discovered a unique mechanism for repairing spinal cord injuries using stem cells in axolotls. Its study can help in the creation of methods for treating patients with similar injuries.
The spinal cord is one of the main components of the central nervous system: it conducts impulses from the brain to organs and back. Also, it coordinates simple unconditioned and some autonomic reflexes. Various injuries can cause irreversible damage to the spinal cord, leading to paralysis and sometimes even death.
In most vertebrates, including humans, the spinal cord is unable to regenerate itself after injury. However, there are exceptions. For example, the axolotl (Ambystoma mexicanum), the larva of the tailed amphibian Ambystoma, which may not develop into an adult form, has a remarkable ability to repair the spinal cord after injury. When an axolotl loses its tail for any reason, neural stem cells in the spinal cord migrate to the injury site to regenerate. So far, scientists can only detect this activity a few days after the start of the process.
“Four days after amputation, stem cells within about one millimetre of the injury divide three times as fast as the normal rate to regenerate the spinal cord and replace lost neurons”, – explains Emanuel Cura Costa, co-first author of the study. “What the stem cells are doing in the first four days after injury was the real mystery.”
To study the processes occurring during the first moments of spinal cord regeneration, researchers at Argentina’s National Scientific and Technical Research Council (CONICET) and the Research Institute of Molecular Pathology (IMP), Austria, teamed up to recreate this process in a mathematical model and test their predictions in axolotl tissue using the latest imaging technologies.
Their results, published on the InLife website, show that neural stem cells accelerate their cell cycles by synchronizing. In this case, this process spreads through the spinal cord.
In the spinal cord, cells multiply asynchronously: some actively replicate their DNA before splitting into two cells to support growth, and some are dormant.
In a new study, scientists have shown that this situation reverses after an injury. Most of the cells near the damaged area rapidly move to a specific cell cycle stage to synchronize with the total mass and multiply in concert.
“We developed a tool to track individual cells in the growing spinal cord of axolotls. Different colors label resting and active cells, which allow us to see how far and how fast cell proliferation happens with a microscope”, – says Leo Otsuki, IMP postdoc and co-author of the study. “We were very excited to see the match between the theoretical predictions and the experimental results.”
The synchronicity of cell division in the regenerating spinal cord is an exceptional case among animals. How can stem cells coordinate their actions at a distance that is almost 50 times their size?
Mysterious signal driving regeneration
“Our model made us realize there had to be one or more signals that spread through the tissue from the injury, like a wave, for the area of proliferating cells to expand”, – explains Osvaldo Chara, career researcher at CONICET and group leader of SysBio at the Institute of Physics of Liquids and Biological Systems (IFLySIB). “This signal might act like a messenger and instruct stem cells to proliferate.”
Scientists believe that this mysterious messenger helps reprogram stem cells, increasing their division rate to repair lost tissue. In a new study, it was possible to find the location of this signal in space and time, paving the way for further study of its characteristics.
“Combining mathematical models with our expertise in tissue imaging was key to understanding how the spinal cord starts regenerating”, – said Elly Tanaka, a senior research fellow at IMP. “The next step is to identify the molecules that promote regeneration of the spinal cord- that could have tremendous therapeutic potential for patients with spinal injuries.”