Thank for you for visiting my new blog. I’m Catriona Cunningham, a third year PhD student at the University of Manchester on the EPSRC and MRC Centre for Doctoral Training (CDT) Regenerative Medicine Programme. I previously studied Medicine with an intercalated BSc (Hons) in Neuroscience with Psychology at the University of Aberdeen. If you want to hear more about that, check out my about page. TLDR- here’s my entry to the Postgraduate Summer Research Showcase Short Film Awards from last year:
In one sentence, my PhD project is looking at using stem cells to repair the injured brain after stroke. A stroke happens when there’s a disruption in the blood supply to the brain and without oxygen, brain cells begin to die. To add insult to injury, inflammation (usually part of the body’s defence mechanism to infection) goes on to cause further damage. Patients that survive their stroke can be left with long term disability including paralysis, speech difficulties and memory impairment. Another problem is post-stroke depression which affects 30-40% of patients and leads to poorer rehabilitation outcomes. There are two types of stroke: ischaemic, caused by a blood clot and haemorrhagic, caused by a bleed in the brain. I work on the former which account for around 85% of cases. The only approved therapy we have in UK right now for ischaemic stroke is alteplate, a drug that breaks down the blot clot to restore the blood supply to the brain. However, only around 5% of patients get this therapy because it has to be given within such a narrow time window (less than 4.5 hours of stroke onset) and even those that do can be left with long-term disability.
There is, as you can appreciate, a massive need for a regenerative therapy for stroke and that’s where my project comes in. I work with mesenchymal stem cells (MSCs), a type of adult stem cell we all have in our fat tissue, bone marrow and dental pulp (connective tissue in the centre of teeth). It was first thought that stem cell therapies for stroke would maybe work by replacing the dead and dying cells. However, in pre-clinical stroke models it’s been shown that that’s not really the case. Only a small percentage of stem cells injected into the bloodstream make it to the brain and then an even smaller percentage of those survive and turn into brain cells. Despite this, stem cell treatment still improved recovery after stroke.
So, why do stem cells work then? We think it could be the secretome (essentially all the molecules cells poop out). MSCs secrete lots of cytokines (small proteins cells use to communicate with each other) that can decrease harmful inflammation after stroke and growth factors that can help repair the injured brain by increasing formation of new brain cells and blood vessels. In my lab, we’re particularly interested in how we can modify the MSC secretome to make a better therapy for ischaemic stroke. Earlier this year we published a paper showing that if you give the MSCs a pro-inflammatory stimulus, they secrete more anti-inflammatory cytokines and growth factors. If you’re really interested you can read the paper here.