How does it work?

One of the central unsolved mysteries of neuroscience is the inability of the central nervous system to regenerate itself. In recent years cell therapy, alongside neuroprotective and neuroregenerative treatments, has emerged as a promising new frontier of treatment in SCI. The rationale for cell transplantation is three-fold. First, that cells transplanted into the spinal cord could replace lost cells, for example replacing the myelin sheath that protects nerves. Second, transplanted cells could secrete growth factors called neurotrophins which would facilitate repair. Third, they could break through the glial scar that walls off the injury, encouraging the regeneration of nerve fibres and helping to restore function.

 

Under your nose

There are a number of promising clinical trials in progress concerning the transplantation both of stem cells and non stem cells. Many studies have focused on the transplantation of Schwann cells – the main glial cells of the peripheral nervous system – which are taken from the patient’s nasal cavity. “Schwann cells can facilitate some aspects of regeneration, and they carry the advantage that they can be harvested directly from the patient,” says Dr Fehlings. “However, they’re limited by the fact that they’re not stem cells. Stem cells have the advantage of being multipotent i.e. they can develop into more than one cell type and are capable of self-renewal. While olfactory cells can mimic some of the functions of the lost cells, they cannot reproduce them.”

 

Embryonic Stem Cells

Yet while stem cells may be our bodies’ secret weapon in self-repair, their application in regenerative medicine is by no means straight forward. “There are many types of stem cell, with Embryonic Stem Cells (ESCs) being the most well-known,” says Dr Fehlings. “In the embryo these can develop into any cell in the body, but in a clinical setting they’re rarely used to directly treat SCI because of the high chance of tumor formation. Instead, researchers take primitive stem cells and culture them under controlled conditions into adult neural stem cells. These are multipotent but are committed to only making nerve cells, which by and large is exactly what we want.”

 

In 2009 Geron Corporation was given FDA approval to launch the world’s first ESC human trial, but financial constraints brought the program to an early demise after just three years.

Stem cell breakthrough

Embryonic stem cell research is an area couched in ethical debate and lacking in committed funding, but there have been significant recent developments in the use of induced Pluripotent Stem Cells (iPSCs), which are adult cells that have been genetically re-programmed to an ESC-like state. In 2012, Japanese stem cell researcher Shinya Yamanaka received the Nobel Prize for his discovery that mature cells can be reprogrammed to become pluripotent. “This is anticipated to be a transformative technological advancement that will avoid ethical challenges and open up the potential for patient-specific therapies,” says Dr Fehlings. “However there’s still work to do.”

 

Promising results

And work is certainly underway, with clinical trials exploring the use of Mesenchymal Stromal Cells (MSCs) derived from bone marrow or the umbilical cord; Olfactory Ensheathing Cells (OECs) from the nasal cavity; and Neural Stem Cells (NSCs) from the nervous system. Each shows promising early results.

 

Indeed, Dr Fehlings was lead investigator for the University of Toronto on a clinical trial sponsored by StemCells, Inc. of California that was the first in North America to use adult neural stem cells to treat spinal cord injury. The trial found compelling evidence that neural stem cells could be effective in remyelinating neurons in the spinal cord.

 

Combined strategies

 “There have been some exciting breakthroughs but it’s a complex field, and it’s likely that successful spinal cord regeneration will require a mix of strategies,” says Dr Fehlings. “At the primary stage of injury, it’s broadly accepted that early decompression surgery and stabilization of the spine greatly improve patient outcomes. However, in the secondary phase the damage is amplified by the onset of ischemia, which reduces blood supply and triggers an influx of sodium, calcium and glutamate.”

 

A new neuroprotective strategy is required to minimise secondary damage.  To do so, a collaborative study is co-funded by AOSpine and explores the potential neuroprotective effect of a drug called Riluzole in minimizing the damage caused by sodium (RISCIS study). Another example is a clinical trial on the use of Cethrin to enhance regenerative capacity.

 

Brighter outlook

“There’s a great deal of interesting work going on,” says Dr Fehlings. “A few years ago, an AOSpine survey revealed that SCI is the number one priority for surgeons in its network. It’s encouraging that treatment options have evolved considerably in the past five years, with a corresponding improvement in patient prognosis.

 

“Spinal injuries aren’t as common as cancer or heart disease, but they’re disproportionately expensive to the healthcare system (the lifetime cost of treating an adult with a severe SCI is in the millions) and they have a devastating impact on the patient and their family. I believe that the progress we’re making in the field of regenerative therapeutics is a realistic source of hope.”