Stem Cell Secretome: a potential new therapeutic for ischaemic stroke

Aims: To assess the therapeutic efficacy of secretome obtained from endothelial progenitor cells (EPCs), preconditioned by exposure to few pathophysiological conditions, notably hypoxia, in restoring cerebrovascular integrity and function during subacute and chronic phases of ischaemic stroke.

Background: Ischaemic strokes occur due to an interference with blood supply to the brain and is characterised by appearance of brain oedema and neurological deficits. Thrombolysis (blood clot dissolution) with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease. However, due to a short therapeutic window i.e. the first 4.5 h of symptom onset, globally less than 1% of patients receive this therapy each year. Hence, discovery of new therapeutics that can prevent the vascular leak while concomitantly inducing neurogenesis and vasculogenesis during subacute and chronic phases of stroke continues to be of paramount importance. We hypothesise that EPC secretome, enriched with a large number of growth factors, cytokines, chemokines, may be one such therapeutics.

Experimental methods: EPCs will be obtained from the human peripheral blood and characterised via specific assays assessing their migratory, proliferative and tubulogenic capacity. Secretome will be obtained from EPCs exposed to few pathophysiological conditions such as hypoxia or pro-inflammatory cytokine, TNF-a. The impact of different secretomes will first be assessed on a well-established laboratory model of human blood-brain barrier. Transient focal ischemia will then be induced in rats by transient middle cerebral artery occlusion before treatment with the most efficacious secretome samples. Therapeutic impact of secretome on neuro-vasculature will be studied by measurements of lesion volume and brain water content (oedema), a marker of blood-brain barrier damage. Sensory motor deficits and cognitive deficits, assessed by lateralised adjusting steps and the novel object recognition tasks will further reveal the therapeutic value of secretomes. The effect of secretome on cerebral and systemic oxidative stress and inflammatory responses will be tested using a variety of sophisticated molecular biological methods like multi-analyte ELISArrays.

Expected outcomes and impact: Data generated will demonstrate whether a cell-based but cell-free therapeutic approach with EPC secretome will restore normal neurovascular function in a clinically relevant model of ischaemic stroke.

How to apply

International students only

Please email a recent CV along with a cover letter to Dr Ulvi Bayraktutan.