Review of Exosomes for restorative therapy in stroke and neurological injury

Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury

Abstract
Stroke is a leading cause of disability worldwide, and brain injuries devastate patients and their families, but currently, no drugs on the market promote neurological recovery. Limited spontaneous recovery of function as a result of brain remodeling after stroke or injury does occur, and cell-based therapies have been used to promote these endogenous processes. Increasing evidence is demonstrating that the positive effects of such cell-based therapy are mediated by exosomes released from the administered cells and that the microRNA cargo in these exosomes is largely responsible for the therapeutic effects. This evidence raises the possibility that isolated exosomes could be used alone as a neurorestorative therapy and that these exosomes could be tailored to maximize clinical benefit. The potential of exosomes as a therapy for brain disorders is therefore being actively investigated. In this Review, we discuss the current knowledge of exosomes and advances in our knowledge of their effects on endogenous neurovascular remodeling events. We also consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury, and other diseases in which neurorestoration could be a viable treatment strategy.

Key points

• Exosomes are involved in many aspects of normal brain physiology and facilitate communication between brain cells and between the brain and the periphery.
• Increasing evidence suggests that exosomes from mesenchymal stromal cells (MSCs) mediate the beneficial effects of cell therapy for stroke and traumatic brain injury
  (TBI).
• The effects of MSC- derived exosomes alone have the potential to improve neurological outcomes in animal models of stroke, TBI and other neurological diseases.
• Of the cargo in exosomes, microRNA (miRNA) is of prime importance in mediating the therapeutic effects.
• Compared with naive MSC- derived exosomes, engineered MSC- derived exosome that contain selected miRNA have more potent therapeutic effects in stroke and TBIs.

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