Now that Asterias Biotherapeutics’ CIRM-funded, stem cell-based clinical trial for spinal cord injury (SCI) has safely treated its first group of patients and begun recruiting the second, should other SCI researchers close up shop? Of course not. Since it’s a first-in-human trial, there certainly will be room for improvement even if the therapy proves successful. And it may not work for every SCI victim. So the development of other therapeutic approaches is critical to ensure effective treatments for all patients with this unmet medical need.
Enter the lab of Michael Fehlings at the University of Toronto. Their recent Stem Cells Translational Medicine study describes a potential, minimally invasive therapeutic strategy which involves a type of brain cell not previously studied in the context of SCI.
In the case of the Asterias trial, embryonic stem cell-derived cells called oligodendrocytes are being transplanted directly into the injured spinal cord to help restore the disrupted nerve signals that cause a whole range of debilitating symptoms, including painful tingling and loss of movement in arms and legs, loss of bladder control and difficulty breathing.
Instead of trying to directly repair the disconnected nerve signals, Fehlings’ team looked at reducing the damaging effects of inflammation that occur at the site of injury in the days and weeks following the spinal cord trauma. This sounds like a perfect job for mesenchymal stem cells (MSCs) whose anti-inflammatory effects are well established. But previous animal studies using MSCs for spinal cord injury have had mixed results. Different sources of MSCs are known to have different anti-inflammatory actions so perhaps this is the culprit behind the variability. On top of that, the exact mechanism of action isn’t well understood which presents a barrier to getting FDA approval for clinical trials.
So the current study performed a careful comparative analysis of the healing effects of human cord blood MSCs and human brain vascular pericytes (HBVPs) – MSC-like cells found near blood vessels in the brain – in a rat model of spinal cord injury. Shortly after the SCI injury, the cells were delivered into the rats through the blood. The blood levels of various cytokines – proteins that modulate the inflammation response – were measured for several days. The only cytokine that increased in the days after the cell delivery of either cell type was IL-10 which is known for its anti-inflammatory effects.
Examining the spinal cord one to seven days after injury, the researchers found that both MSCs and HBVPs were better than controls at reducing hemorrhaging, with the HBVPs showing better improvement. In terms of long-term effects on functional behaviors, the researchers showed that after three weeks, grip strength, body coordination, and hind limb movement were most improved in the HBVPs.
In a university press release, Fehlings described these promising results:
“Our study demonstrates that these cells not only display a MSC phenotype in a dish, but also have similar immunomodulatory effects in animals after spinal cord injury that are more potent than those of non-central nervous system tissue-derived cells. Therefore, these cells are of interest for therapeutic use in acute spinal cord injury.”
A lot more work will be needed to translate these findings into clinical trials but for the sake of those suffering from spinal cord injury it’s encouraging that alternative approaches to treating this devastating, life-changing condition are in development.