Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Abstract

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

Keywords: bioengineering; blood-brain barrier; cell therapy; hypoxia; ischemic stroke; personalized treatment; preconditioning; secretome.

Figure 1

Molecular effects of MSC-EVs on various cells in the neurovascular unit (NVU) in stroke. MSC-EVs and its contents affect diverse molecular pathways in endothelial cells, microglia, astrocytes, neurons and pericytes. They regulate various processes such as angiogenesis, tight junction integrity, pericyte migration, neurite outgrowth, neurogenesis, and microgial polarization. These complex interactions between different cell types determine the neurological outcome after stroke. Dotted lines indicate inhibition, while solid lines indicate potentiation.