Clearance of Senescent Cells as an Approach to Limit Scar Formation in Nerve Injury

Senescent cell behavior following injury is different and the clearance of these cells much more efficient in species like zebrafish and salamanders capable of regrowing organs. Researchers here suggest that senolytic therapies to selectively destroy senescent cells could be used in mammals to limit the scar formation that follows nerve injury, an important goal in enabling regrowth and restoration of nerve function. Their particular interest is spinal cord injury, their work should be applicable to the rest of the nervous system as well.

Mammals have a poor ability to recover after a spinal cord injury which can result in paralysis. A main reason for this is the formation of a complex scar associated with chronic inflammation that produces a cellular microenvironment that blocks tissue repair. Researchers have now shown that the administration of drugs that target specific cellular components of this scar can improve functional recovery after injury.

Researchers have been studying spinal cord injury using two different models: the zebrafish, where there is spinal injury recovery, and mammals that show poor recovery. The dense scar that forms at the lesion site has been of particular interest. In mammals, upon spinal cord injury, researchers observed that cells start to accumulate at the lesion periphery. But not any cells: "These cells are known as senescent cells. They have specific features and markers and are what we can call 'zombie cells', where growth and division is interrupted, but where the normal cell death program is not activated."

"While in zebrafish, the accumulation of these cells at the injury periphery is cleared out over time, in mammals, these cells persist and are important components of the dense scar observed. Because senescent cells have specific molecular markers, there are specific drugs that could be tested in this context. With the administration of different senolytic drugs, that specifically target these senescent cells, we have observed a progressive decrease of these cells, a decrease in the scar extension and lower levels of inflammation due to a decreased secretion of pro-fibrotic and pro-inflammatory factors. The observed changes at the molecular level underlie the improved locomotor, sensory, and bladder functions that we have also found."


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