Title:Current Status of In vitro Models of the Blood-brain Barrier
Volume: 19
Issue: 10
Author(s): Brijesh Shah and Xiaowei Dong*
Affiliation:
- Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North
Texas Health Science Center, Fort Worth, Texas, 76107, USA
Keywords:
Blood-brain barrier, in vitro models, tight junctions, endothelial cells, stem cells, perivascular cells.
Abstract: Disorders of the brain constitute the most debilitating situation globally with increased mortality
rates every year, while brain physiology and cumbersome drug development processes exacerbate
this. Although blood-brain barrier (BBB) and its components are important for brain protection, their
complexity creates major obstacles for brain drug delivery, and the BBB is the primary cause of treatment
failure, leading to disease progression. Therefore, developing an ideal platform that can predict the
behavior of a drug delivery system in the brain at the early development phase is extremely crucial. In
this direction, in the last two decades, numerous in vitro BBB models have been developed and investigated
by researchers to understand the barrier properties and how closely the in vitro models mimic in
vivo BBB. In-vitro BBB models mainly involve the culture of endothelial cells or their coculture with
other perivascular cells either in two or three-dimensional platforms. In this article, we have briefly
summarized the fundamentals of BBB and outlined different types of in vitro BBB models with their
pros and cons. Based on the available reports, no model seems to be robust that can truly mimic the
entire properties of the in vivo BBB microvasculature. However, human stem cells, coculture and threedimensional
models have been found to mimic the complexity of the barrier integrity not completely but
more precisely than other in vitro models. More studies aiming towards combining these models together
would be needed to develop an ideal in vitro model that can overcome the existing limitations and
unravel the mysterious BBB vasculature.