Cerebral ischemia, stem cells, functional recovery

Stroke is the third most common cause of death in the UK and the single most common cause of severe disability with profound effects on patients, relatives and the economy (~£7 billion /year). With an increasing ageing population in the UK and a paucity of licensed therapies for stroke, new therapeutic strategies are needed to prevent brain damage after stroke. Our own and others have highlighted the potential of stem cell therapy for stroke (Patkar et al, 2012). This project focuses on the key questions: How can we improve stem cell function after stroke? We will employ various approaches such as use of biomaterials or enhancing endogenous mechanisms of repair, such as modulation of microglia or interactions with other cells.  

Briefly 3 month old male mice will undergo middle cerebral artery occlusion with reperfusion and 48 hours later mice will undergo stem cell transplantation of stem cells with and without modulation by biomaterials or secretary functions. Behavioural recovery will be used to assess stem cell success after stroke over 4 weeks. Thereafter brains will be assessed for infarct volume and markers of brain plasticity and repair. These experiments may be complemented with in vitro studies.

Expected results and Conclusions: These results are expected to reveal how we can modulate the stem cells to improve their function and also how we can improve stem cell technology to improve therapeutic potential of stem cells in stroke.

Patkar, S., Tate, R., Modo, M., Plevin, R., Carswell, H.V.O. Conditionally immortalised neural stem cells promote functional recovery and brain plasticity after transient focal cerebral ischaemia in mice. Stem Cell Research. 2012 Jan;8(1):14-25