Understanding and design of a novel dynamic biomimetic blood-brain barrier model

Subtitle:gateway to study the ever-evolving concepts related to the neuroinflammation of the central nervous system

Current insights into the recruitment of DC to the CNS and possible underlying mechanisms are primarily based on studies that examine the interaction of DC with epithelial and endothelial cells of non-cerebrovascular origin and on analogies with transmigration of leukocytes other than DC. Despite several information on the increased transmigration of leukocytes following the breakdown of BBB into the CNS, there is still no clear understanding of the underlying mechanism of this process. Only a very few studies have specifically addressed the interaction of DC with BBB endothelial cells and the transmigration process of DC through the BBB. Gaining a better and deep awareness of the molecular mechanisms involved in the process of migration of leukocytes in particular human DCs across the BBB is very much required to constrain their excessive transfer during the various neuro-inflammatory disorders such as MS. In this context, different studies are also now focussing on the establishment of an in vitro model either static or dynamic BBB system to study the movement of human DCs through the barrier formed. Even though diverse transwell and fluidic models of BBB are present in the literature with the incorporation of different cell types constituting the BBB, there is still a need of a simple yet effective system which mimics the exact barrier formed inside the human body to illustrate and understand the increased migratory capacity of pathogenic dendritic cells in detail. Hence, in this research, we have aimed to investigate the trafficking of dendritic cells using an in vitro BBB model and subsequently studying the phenotypic and functional differences between migrating and non-migrating DC. In doing so, we envision elucidating underlying pathological mechanisms that may set a stage for the identification of interesting targets and strategies for therapeutic intervention based on both DC and the process of DC transmigration. The second objective is to come up with the design and details of a physiologically relevant BBB transmigration assay encompassing of a dynamic in vitro BBB model incorporating shear forces that mimic blood flow as observed in the human body. Further implementing this in-house designed microfluidic three-dimensional dynamic model of BBB to mimic the exact properties of the barrier formed inside the human brain can ultimately lead to a much better apprehension of the processes involved in MS further unravelling various targets within DCs to devise appropriate treatment approaches.

Publication year:2022

Keywords:Doctoral thesis

Accessibility:Open