Endothelial progenitor cells: Potential novel therapeutics for ischaemic stroke

Abstract

Stroke is classified into two main groups depending on its aetiology; ischaemic stroke and haemorrhagic stroke which successively develop from the occlusion or rupture of an artery leading to the brain. Despite being the leading cause of human cerebral damage, there is currently no medical therapy for haemorrhagic stroke and thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for ischaemic stroke. However, due to its short therapeutic window (first 4.5 h of stroke onset) and increased risk of haemorrhage beyond this point, globally each year less than 1% of patients receive this therapy. Since, endothelial dysfunction, associated with inflammation and vascular permeability, remains the key early event in the pathogenesis of stroke, endogenous element(s) capable of countering this defect may help maintain vascular homeostasis and explain the overt differences observed in patients' functional outcome. Accumulating evidence indicate that bone marrow-derived endothelial progenitor cells (EPCs) equipped with an inherent capacity to repair endothelial damage and differentiate into few other cell lines represent one such element. Indeed, EPC-based cell therapy, backed by rigorous preclinical, translational and early proof-of-concept, safety and feasibility clinical studies, is now considered as an important novel therapeutic approach. However, several questions relating to optimal cell dosage, delivery route and immediate and sufficient availability of cells remain to be addressed before its efficacious translation to clinical practice. In this context, ex vivo expansion of EPCs leading to an abundant generation of functional outgrowth endothelial cells offers a great opportunity to address these issues and create a novel off-the-shelf type of therapeutic product.

Trial registration: ClinicalTrials.gov NCT02980354.

Keywords: Cell-based therapy; Endothelial progenitor cells; Ischaemic stroke; New therapeutics; Regenerative medicine; Stroke.