How Can Stem Cells Treat Spinal Cord Injuries?

Before we talk about stem cell treatments, lets review some basics.  What is the spinal cord?  The spinal cord is the connection between your brain and the rest of your body.  It originates at the base of your brain, and carries signals to your arms and legs via spinal nerves (with branch off the spinal cord at each vertebre).  It also carries information collected by our body back to the brain, so we know to avoid the hot teapot, for example.  

How is the spinal cord injured? A spinal cord injury can be devastating because it cuts off all contact between your brain and your body below the level of injury.  Remember that your spine is made of vertebrae (a collection of block-like bones stacked on top of each other) and held together by thick ligaments.  The spinal cord runs down the middle of your spine, so the spinal cord is protected by hard bone on all sides.  Yet significant trauma can break one of the vertebrae and allow the spinal cord to become squished, or a bullet or knife can sneak in-between the small space that separates two neighboring vertebrae, and thus injure the cord.  

But injury to the spinal cord does not just happen with the immediate traumatic event, and the injury can continue to occur after the trauma happens due to progressive inflammation and swelling around the site of injury.  The spinal cord is encircled with bone (the vertebrae) which is normally a great protection, yet after an injury, the swelling can build up in this confined space and there is nowhere for the increasing pressure to go, and as a result, it compresses the spinal cord, preventing the nerves from receiving nutrients and oxygen, causing further damage.  

Why is a spinal cord injury so hard to treat? The problem with spinal cord injury is that doctors have not figured out a good way to repair the injured nerves.  They cannot undo the damage that has occurred.  When a bone breaks, it has the ability to heal, so it can undo the damage (same goes for your skin, our cuts form a scab and then a scar over a few weeks).  This is not true with the spinal cord...the nerves are not good at growing back, and so whatever injury occurs, will remain forever (or so we think...).  The best thing that doctors can do currently, is to prevent further injury from occurring after the initial traumatic event.  As we mentioned earlier, often times the body's reaction to the injury (such as inflammation and swelling) is what causes a lot of the injury to the spinal cord, and thus, if spine surgeons act quickly, and decompress the spinal cord after injury (reduce swelling), they can prevent some of this from occurring.  They can also give steroids to reduce inflammation.  Also sometimes they can stabilize the broken vertebral bones to prevent the spine from bending further and squishing the spinal cord even more.  But remember that all this treatment is "damage control" and not repair or reconstruction.  

Is there a future for spinal cord repair? Maybe! The ideal treatment for spinal cord injuries would target the remaining axons (nerves) to stimulate growth, and would target the fibroblasts (generic scar forming cells) to turn them into nerves (because scar has no function, it just occupies space...its like using grout to fill in a crack in your TV...what you really need are Pixels). Stem cells could be the answer, because they are cells in our body that haven't decided what they want to be yet (think of a freshman in college - they can be whatever they want in life) and therefore, could be turned into the nerve cells that were destroyed by the trauma.  To use the college analogy more specifically, stem cells are not all the same, and some stem cells are further along in their studies as others....mesenchymal stem cells are like students in Engineering school...they could still be a lot of different things, but they are definitely not graduating with a degree in pottery (mesenchymal stem cells can eventually become any type of cell in the muscle, bone, or soft tissue, but nothing else).  In contrast, embryonic stem cells are the true freshman that have not chosen any path and could truly become anything.

When stem cells are introduced to certain environmental stimuli (to use the college analogy, think about a freshman taking certain classes to prepare him/her for their desired career) and the cells then become a specific type of cell.  

What can stem cells do in today's world?  Mesenchymal Stem cells (stem cells for the muscle and soft tissue) have been shown in rats to stimulate the growth of living neurons (promote axonal growth) and to reduce harmful inflammation. But they cannot become new nerves.  Mesenchymal Stem cells have been given to patients with spinal cord injury, but the results were mixed (not a home run).  Embryonic Stem cells have been shown in rats to decrease nerve cell death, and stimulate the growth of living neurons.  Importantly, there are studies that suggest this type of stem cell is able to transform into the nerves found in the spinal cord.  There is little study on humans (in large part because of the ethical considerations for embryonic stem cells, and when you believe human life begins), although one study on humans which implanted fetal liver and fetal brain cells, showed some minor improvements.  

Induced-pluripotent stem cells is an area of great interest because it takes mature cells and re-programs them (its like Rodney Dangerfield in "back to school") so that they can behave like embryonic stem cells (without the ethical debate).  Currently there is lab studies in mice that show some success.  

References

1. Frehling MG, Vaccaro A, et al.  Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One. 2012. full article.  Decompression within 24 hours of injury leads to improved outcomes: 2 more more grade improvement in ASIA score, studied 313 pts.

2. Sandner B et al. Neural stem cells for spinal cord repair. Cell Tissue Res 2012; 349 (1): 349-362. full article. goals of spinal cord repair.

3. Ankey DP et al. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol 2004; 190(1): 17-31. full article.

4. Yoon SH et al. Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor. Stemm Cells 2007; 25(8): 2066-73. full article. 

5. Keirstead HS et al. Human embryonic stem-cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 2005; 25(19): 4694-05.  full article. 

6. Schroeder GD et al. The use of cell transplantation in spinal cord injuries. JAAOS 2016; 24(4); 266-75. full article. 

7. Seledtsova GV et al. Delayed results of transplantation of fetal neurogenic tissue in patients with consequences of spinal cord trauma. Bull Exp Biol Med 2010; 149(4): 530-33. full article. 

8. Romanyuk N et al. Beneficial effect of human induced pluripotent stem cell-derived neural precursors in spinal cord injury repair. Cell Transplant 2015; 24(9); 1781-1797. full article.