Posted on Mar 09, 2021, 6 p.m.
Researchers at UT Southwestern and Indiana University led by Chun-Li Zhang, Ph.D., professor of molecular biology at UT Southwestern, are proposing a method of harnessing the Sox2 stem cell protein known to proliferate after a spinal cord injury to promote healing.
Genetic engineering allowed the team to reprogram specific NG2 glia cells to overproduce Sox2 in mouse models of spinal cord injury. The report published in the journal Cell Stem Cell describes how within weeks the re-engineered cells produced mature neurons that cont
The brain has some limited ability to produce new nerves cells using progenitor cells to turn on distinct regenerative pathways; while examining injured spinal cords in animals for similar markers that would normally exist in immature neurons, a marker was discovered that is produced by NG2 glia non-neuronal cells that make oligodendrocytes, which in turn generate a layer of protective fat that surrounds neurons.
NG2 glia are also what forms scar after a spinal cord injury, taking on some properties of immature neurons, but the mechanism as to how was unclear. To investigate how NG2 glia was genetically manipulated to remove the ability to make Sox2. In mice with this alteration fewer immature neurons were observed after spinal cord injury, providing a clue that Sox2 helped NG2 glia to make the neurons.
Next NG2 glia was engineered to overproduce Sox2 in mouse models of spinal cord injury. Animals with this alteration were observed to produce tens of thousands of neurons, and those cells formed new connections with existing neurons, which is a key step in restoring signals between the brain and the rest of the body. When the altered animals were compared to those making normal amounts of the protein, the altered animals were observed to perform better in tasks used to measure motor skills, and they also formed less scar tissue than the control mice did.
Sox2 is a transcription factor that is able to turn genes on/off that has attracted a lot of interest among those studying a variety of diseases, such as a Harvard team discovering that the gene making Sox2 plus two additional genes delivered into the retinas of mice boosted the population of neuron involved in vision.
In another study Zhang found that injecting Sox2 into the brains of mice led to an increase in cells that function similar to dopaminergic neurons, prompting investigation as a potential treatment for Parkinson’s disease and related brain disorders. As for engineering Sox2 to treat spinal cord injuries, Zhang said that more research is required to find an effective and safe way to over-produce it in humans, but the initial idea holds promise.
"The field of spinal cord injury has extensively researched trying to heal the damage with stem cells that produce new neurons, but what we're proposing here is that we may not need to transplant cells from the outside," Zhang said in a statement. "By encouraging NG2 glia to make more Sox2, the body can make its own new neurons, rebuilding from within."
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