Description of research
The brain is essential for almost all of our normal functions. Stroke is a leading cause of death and disability and most commonly occurs when blood flow to the brain is interrupted by a clot blocking a blood vessel in the brain. Damage to the brain that occurs during a stroke can result in significant disability and sometimes death.
Inflammation is an important defence mechanism that the body uses in response to injury or infection. However, it can also be highly damaging to the body and contribute to disease. In the case of stroke, inflammation inside and outside of the brain has been shown to cause additional damage to the brain early after the stroke has happened. A molecule called interleukin-1 (or IL-1 for short) is produced by brain cells during the stroke and goes on to kill other brain cells.
A new type of adult stem cell called mesenchymal stem cells (MSCs) has the potential to improve recovery after stroke. Previous research has found that the environment of MSCs can be modified and IL-1 used to make them better at protecting the brain and stimulating repair and recovery after a stroke.
The current study aims to exploit these recent discoveries by testing whether MSCs can limit inflammation, repair the brain and recover normal brain functions after stroke using clinically relevant mouse models (which can mimic the conditions of a stroke in humans).
It is hoped that this research could lead to the use of modified MSCs in future stroke therapies in patients.
What are the researchers aiming to do?
This study aims to test whether MSCs can limit inflammation, repair the brain and recover normal brain functions after stroke. The researchers will test MSCs in mice models of stroke, which is an important step before therapies can be tested in humans.
The MSCs being tested have been modified with a molecule called interleukin-1 (IL-1). This is an inflammatory molecule that is produced by the brain during stroke. Inflammation is an important defence mechanism that the body uses in response to injury or infection. However, in stroke, inflammation has been shown to cause additional damage to the brain.
So what happened?
This research found that injecting modified MSCs into an artery leading to the brain can promote recovery after stroke. This treatment method could be used with, and potentially increase the effectiveness of thrombectomy. The researchers are now planning to secure funding to test the safety and efficacy of these MSCs in stroke patients.
The researchers either injected MSCs that had been modified by exposure to IL-1, MSCs that had not been exposed or the injection medium without MSCs (the vehicle) into the artery of mice that had stroke caused by a blood clot. They looked at various markers of stroke recovery in the short term (3 days) and the longer term (14-days) after stroke.
They found that in mice injected with modified MSCs compared to the vehicle, there was:
- A significantly reduced amount of damaged brain tissue and neurological deficits detected.
- No difference in nest building behaviour or burrowing test, which are indicators of well-being.
- Better recovery indicated by weight assessment, but only at the longer term time point.
They also found that MSCs that had not been exposed to IL-1 reduced brain damage and neurological deficits in the shorter term compared to where the vehicle was injected, but this was not significant.
The researchers looked at markers in brain tissue for growth of new neurons (neurogenesis) or blood vessels (angiogenesis), inflammation and distribution of MSCs. In mice treated with modified MSCs:
- There wasn’t a significant difference, but a trend of more newly generated neurons and cells that line blood vessels.
- There also wasn’t a significant difference in most markers of inflammation, except a reduction in IL-6 in the lungs.
- They were detected in brain vessels, which means MSCs travelled from injection site in the artery to the brain.
Finally, blood flow in the brain was not found to be altered and there wasn’t an increased number of clot-forming cells (platelet aggregates). This suggests MSCs don’t increase the risk of blood clot formation.
Therefore the researchers conclude that MSCs modified by exposure to IL-1 could be a promising treatment for stroke patients. They are now planning to secure further funding to test this.
The researchers published a paper reporting on this research that can be found here:
A second paper is in preparation to be published in Translational Stroke Research.