A major breakthrough in science! Development of brain-like organs that can predict the potential of drug permeability

, June 16, 2020 /
BiovalleyBIOON/-- The human brain is bathed in a supportive fluid called cerebrospinal fluid (CSF), which provides nutrients and is necessary for the brain to function properlyDue to the lack of experimental means, little is known about the composition of human cerebrospinal fluid and how it is formedThe Madeline Lancaster team at the LMBCell Biologyat the MRC Molecular Biology Laboratory at the University of Cambridge has now developed a new brain device that can produce cerebrospinal fluid and has the potential to predict whether the drug will enter the braincerebrospinal fluid is produced and secreted by a vein plexus (ChP) deep in the brainChP also filters the blood as a barrier to prevent most substances transported in the blood from entering the brain, while selectively allowing certain small molecules to enterTo study the development and function of human ChP, including how cerebrospinal fluid is formed, Madeline's team developed a new organ-like model of the tissueImage Source: MRC Laby of Molecular BiologyOrgan?organ is a collection of organ-related cell types produced bystem cellsand can be studied as simplified micro-organsOrgan-like organs show cell types similar to those they simulate and perform certain functionsscientists use signaling molecules to directstem cellsto specific types of cells to make organ-like organs, similar to how tissues are produced during developmentto develop a human-CSF culture model, Laura Pellegrini of the Lancaster Group has developed a scheme to produce ChP-type organs from humanstem cellbased on the team's method of producing brain-like organsThese organisms exhibit key features of human ChP and separate CSF-filled chambers from surrounding mediabrain organs with potential to predict drug permeability
the team found that the liquid contains known biomarkers of cerebrospinal fluid, which were able to observe changes in cerebrospinal fluid composition over time and the different cell types that cause dynamic changes in cerebrospinal fluid compositionImportantly, they found a previously unrecognized cell type in ChP: myocutancortex cellsThese cells may be responsible for producing important mechanical forces related to CSF secretionChP-like organs have also been found to form a tight barrier that shows the same selectivity towards small molecules, just like ChP seen in the brainFor example, they block the entry of the small molecule dopamine, but allow the transport of its precursor L-DopaThis proves the accuracy of the model about the tissue it represents, which means that ChP-type organs can predict the permeability of new drugsTo prove this, the team studied a drug that recently failed in theof phase Iclinical trials -- BIA-10-2474 -- and reported that organ-like organs could predict inappropriate accumulation of drugs and lead to neurotoxicity the composition of the brain barrier varies by species, the development of a ChP model for humans is important for predicting the penetration of new drugs and reducing the number of new drugs that fail in phase i clinical trials This model is also the source of more realistic cerebrospinal fluid specially made by ChP tissue This will allow scientists to study the secretion of factors with unclear functions and disease-related biomarkers (BioValleyBioon.com) References: Laura Pellegrini et al.
Human CNS barrier-forming organoids with cerebrospinal fluid , Science (2020) DOI: 10.1126/science.aaz5626
Brain organoids with the potential to the predict drug-dwelling