Challenging the great vascular wall: Can we envision a simple yet comprehensive therapy for stroke?

Stroke is a leading cause of death in adult life, closely behind ischemic heart disease, and causes a significant and abiding socioeconomic burden. However, current therapies are not able to ensure full neurologic and/or sequelae-free recovery to all stroke survivors. We believe treatment efficacy and patient rehabilitation could be enhanced significantly by targeting blood-brain barrier (BBB) deregulation and inflammation-induced barrier loss that occurs after stroke. In this pathological context, bone marrow-derived endothelial progenitor cells (EPC) enter the bloodstream towards the lesion site, but their insufficient numbers and impaired angiogenic ability compromise neurovascular regeneration. In this context, cell-based therapies have become increasingly appealing since treating patients with large numbers of mesenchymal or hematopoietic stem/progenitor cells alone may boost repair. However, this approach could be met with several challenges in terms of logistics and cost; hence, the development of a drug delivery system suitable for intravenous administration and functionalized for selective uptake by circulating EPC could enhance their restorative potential without perceived complications. The ability to encapsulate proangiogenic and anti-inflammatory agents, such as retinoic acid, and to safely and easily deliver them systemically may open new therapeutic perspectives for the treatment of cerebrovascular disorders.