Researchers at Ben-Gurion University of the Negev, Israel, and Cedars-Sinai Medical Center, US, have, for the first time, replicated a patient’s blood-brain barrier (BBB) by creating a human BBB chip from stem cells, which can be used to develop personalised medicine and new techniques to research brain disorders.

Precision medicine 2019

The BBB protects the brain by blocking toxins and other foreign substances in the bloodstream from entering brain tissue. However, it can also prevent therapeutic drugs from reaching the brain. Neurological disorders such as multiple sclerosis, epilepsy, Alzheimer’s disease, and Huntington’s disease, which collectively affect millions of people worldwide, have been linked to defective BBBs that block biomolecules needed for healthy brain activity.

The researchers genetically manipulated blood cells collected from an individual into stem cells, which are used to create the various cells that comprise the BBB. The cells are placed on a microfluidic BBB organ-chip, which is approximately the size of an AA battery. This chip is made up of hollow channels lined with tens of thousands of living human cells and tissues. This living, micro-engineered environment recreates the natural physiology and mechanical forces that cells experience in the body.

The living cells recreate a functioning BBB, including blocking the entry of certain drugs. Significantly, when this BBB was derived from cells of patients with Allan-Herndon-Dudley syndrome — a rare congenital neurological disorder — and Huntington’s disease patients, the barrier malfunctioned in an identical way to that of the BBB of patients with these diseases, thus generating a personalised model of the human BBB and allowing for the prediction of which brain-affecting drug is best suited to the individual patient.

The study’s findings create dramatic new possibilities for precision medicine and are of particular importance for neurological diseases like epilepsy or schizophrenia, for which several FDA-approved drugs are available, but current treatment selections are largely based on trial and error. These findings may also lead to advances in drug screening and could be used to identify how investigational compounds for neurological disorders interact with the BBB.

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