Scientists Use Patient Cells, Chip Technology to Re-create Blood-Brain Barrier Defects

Researchers at California’s Cedars-Sinai Medical Center have re-created the blood-brain barrier, a vital component of the central nervous system, using Organ-Chip technology by Emulate. This advances the possibility of patient-specific treatments for neurodegenerative disorders, including  amyotrophic lateral sclerosis (ALS).

Blood-brain barrier defect has been linked to ALS and other neurological conditions.

The laboratory generated blood-brain barriers that not only are structurally similar but also function as they would in individuals whose cells were used to re-create it, the study found.

“The study’s findings open a promising pathway for precision medicine,” Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and a senior author of the study, said in a press release.

The study, “Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications,” was published in the journal Cell Stem Cell.

The function of the blood-brain barrier is to protect the brain from toxins, pathogens, and other foreign substances that may be present in the bloodstream. It also prevents therapeutics from reaching the brain. A faulty blood-brain barrier that also keeps out natural biomolecules required for proper functioning of the brain has been linked to several neurological conditions, including ALS, Huntington’s Disease, and Parkinson’s disease.

Researchers obtained blood samples from volunteers and isolated a particular type of cells called induced pluripotent stem cells (iPSC) from the blood. The iPSCs are stem cells that can develop into any type of cell.

Using iPSCs, the team generated all the components of the barrier (nerve cells, blood vessels, and other support cells). However, for all the components to interact with one another and function as they do in the body, they must be in conditions similar to their natural environment in their original location. For this, the team used organ-chips developed by Emulate. Organ-chips are AA battery-sized transparent units that re-create the body’s microenvironment and flow of blood and air.

Once placed in the organ-chips, the cells formed a tight single layer of the functional unit and worked as a blood-brain barrier just as they would in the body. The barrier also expressed biomarkers (proteins) specific to the brain and prevented the entry of certain therapeutics, the team found.

The researchers also used iPSCs derived from blood samples obtained from patients with Huntington’s disease or another rare brain development disorder called Allan-Herndon-Dudley syndrome in this study. The resulting blood-brain barrier exhibited characteristics specific to the condition, such as the absence of specific protein channels and compromised barrier integrity. It malfunctioned the same way as seen in patients with Huntington’s disease and Allan-Herndon-Dudley syndrome.

“By combining Organ-Chip technology and human iPSC-derived tissue, we have created a neurovascular unit that recapitulates complex [blood-brain barrier] functions, provides a platform for modeling inheritable neurological disorders and advances drug screening, as well as personalized medicine,” the authors wrote.

This study is the result of the collaborative Patient-on-a-Chip program between Cedars-Sinai and Emulate started in February 2018 and initiated by Cedars-Sinai Precision Health. The goal of the program to develop personalized, effective therapies based on the patient’s genetic makeup.

“The possibility of using a patient-specific, multicellular model of a blood-brain barrier on a chip represents a new standard for developing predictive, personalized medicine,” Svendsen said.