"Blood brain barrier on a Chip Model" for the study of drug delivery to the central nervous system
Lead Research Organisation:
University of Nottingham
Department Name: School of Veterinary Medicine and Sci
Abstract
A useful BBB in vitro model should meet the following criteria: reproducibility of solute permeability, display of a restrictive paracellular pathway and physiologically realistic architecture, functional expression of transporters, and ease of culture. Co-cultures of brain endothelial, astrocytes and pericytes have led to high expression of BBB transporters and tight junctions, however, it has been shown recently that including hemodynamic flow into the co-cultures leads to a more realistic representation of the BBB. The Wyss Institute at Harvard University gave a press release in 2016 that they had created a 3-dimensional in vitro model of the human BBB "on-a-chip." which automatically oriented itself in a permutation similar to what is seen in vivo when put in the same environment
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/R50628X/1 | 01/10/2017 | 31/12/2021 | |||
| 1981091 | Studentship | BB/R50628X/1 | 01/10/2017 | 30/09/2021 | Chloe Whitehouse |
| Description | The lack of effective treatments for brain diseases is a prominent issue within our society. With eight hundred thousand people in the UK suffering with dementia, one in four adults experiencing a mental health problem each year, and nearly half of adults suffering from a form of chronic pain, the need for effective drugs has never been higher. However, research into new drugs to treat brain diseases is an unfavourable investment for pharmaceutical companies due to the high failure rate of brain-targeted drugs in clinical trials. This high rate of failure can be partly attributed to the difficulty in designing drugs that can pass from the blood circulation into the brain. The restrictive "blood-brain barrier" lines the inside of all blood vessels in the brain. This creates a nearly unsurpassable hurdle for chemical compounds to cross, and thus renders 98% of new drugs ineffective. As such, models of the human blood-brain barrier are currently used when designing a new drug to test if the chemical compound is able to enter the brain and, in theory, allows elimination of ineffective candidates. However, the models currently in use are notoriously inaccurate and unreliable. A model of the blood-brain barrier which could accurate predict the drugs that will enter the brain would save both money and time in the development process, and thus make investment into drugs for brain diseases more favourable. Therefore, the aim of this project was to create a model which mimics the restrictive nature of the living human blood-brain barrier. In this project so far, we have practised a technique to isolate the blood vessels from pig brains that would otherwise be going to waste from commercial abattoirs. These blood vessels are then grown under controlled conditions to maintain the blood-brain barrier outside of the natural living environment. Analysis of the genes expressed by the cells forming the blood vessels have shown that they retain their blood-brain barrier characteristics for several days outside of the body. Therefore, our Key Findings so far are that an in vitro blood-brain barrier can be formed by pig brain blood-vessels, and that this blood-brain barrier can retain some of its living properties for a limited period of time. |
| Exploitation Route | This project is still ongoing, so the further work to be carried out in the project includes growing the blood-brain barrier cells inside of an artificial channel inside a plastic microchip to form a partly biological and partly synthetic blood vessel, known as a blood-brain barrier "on-a-chip". This synthetic blood vessel will be fed with a nutrient-dense solution, creating a false blood flow to mimic that which the cells would experience in the living brain. We aim to evaluate the accuracy of the blood-brain barrier "on-a-chip" model by comparing data on the transport of current human drugs to data taken from studies in living humans and pigs. |
| Sectors | Pharmaceuticals and Medical Biotechnology |