Human <i>in vitro</i> models of neurovasculature and the application to pre-clinical intracerebral haemorrhage research.

Abstract

Haemorrhagic stroke continues to be a leading cause of death and disability globally, with limited treatment options. Pre-clinical models must adapt to offer translationally relevant and physiologically accurate alternatives to animals. The development of complex co-culture blood-brain barrier models and the incorporation of hydrogels and biomaterials has resulted in microphysiological 3D platforms. Amongst such 3D platforms, cerebral organoids have transformed the field of neuroscience. Additionally, emerging techniques for vascularisation and perfusion now provide, for the first time, an entirely human-based model of the cerebrovasculature. In this review, we explore the relevance of various <i>in vitro</i> platforms - such as transwells, hydrogels and other biomaterials, microfluidics, spheroids, organoids, and perfusion-based systems - for pre-clinical research into haemorrhagic stroke. We discuss the advantages and limitations of each model, with a particular focus on the aspects of disease pathophysiology that hold promise for clinical translation. With some adaptation, intracerebral haemorrhage research can benefit from these models for elucidating pathology and recovery mechanisms that can be exploited therapeutically.