Pericyte derivation and transplantation for blood-CNS barrier reconstitution in CNS disorders

Abstract

Disruption of the blood-central nervous system barrier (BCB) is increasingly recognized as a pathological factor in diseases and trauma of the central nervous system. Despite the neuropathological impact, current treatment modalities do not target the BCB; strategies to reconstitute the impaired BCB have been restricted to nutritional and dietary remedies. As an integral cell type in the neurovascular unit, pericytes are crucial to the development, maintenance, and repair of the BCB. As such, pericytes are well poised as cellular agents for reconstitution of the impaired BCB. Here, we summarize recent revelations regarding the role of BCB disruption in diseases and trauma of the central nervous system and highlight how pericytes are harnessed to provide targeted therapeutic effect in each case. This review will also address how recent advances in pericyte derivation strategies can serve to overcome practical hurdles in the clinical use of pericytes.

Keywords: Adult stem cells; Blood-CNS barrier; Cell therapy; Pericytes.

Fig. 1

Components of the blood-CNS barrier and CNS pericyte functions. Situated at the interface between the vascular system and the CNS, CNS pericytes embedded in the basement membrane are a crucial part of the neurovascular unit.

Fig. 2

Therapeutic effects of pericyte transplantation and its clinical applications. Pericyte loss or dysfunction is observed in neurodegenerative diseases, neurotrauma, and stroke. Due to its multifaceted functional profile and high relevance in various CNS pathology, pericyte transplantation is an attractive therapeutic agent that is also broadly applicable.