Scientists recreate an abnormality of the blood-brain barrier on the outside of the body



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Scientists can not create a living copy of your brain outside of your body. This is the substance of science fiction. But in a new study, they recreated an essential component of the brain, the blood-brain barrier, that functioned as it would in the individual who provided the cells to make it. Their achievement – detailed in a study published today in the peer-reviewed journal Cell strain cell – provides a new way to make discoveries about brain disorders and, potentially, to predict which drugs will be best for a given patient.

The blood-brain barrier acts as an access controller by preventing toxins and other foreign substances in the blood from entering the brain tissue and damaging it. This can also prevent potential therapeutic drugs from reaching the brain. Neurological disorders such as amyotrophic lateral sclerosis (Lou Gehrig's disease), Parkinson's disease, and Huntington's disease, which collectively affect millions of people, have been badociated with poor blood-brain barriers that prevent the penetration of the necessary biomolecules. to healthy brain activity.

For their study, a team led by researchers at Cedars-Sinai has generated stem cells known as induced pluripotent stem cells, which can produce any type of cell, using the blood samples of 39, an individual adult. They used these special cells to make neurons, blood vessel liners, and support cells that together make up the blood-brain barrier. The team then placed the different cell types inside organ chips, which restored the body's microenvironment with the natural physiology and mechanical forces experienced by cells in the body. human body.

Living cells have quickly formed a functional unit of the blood-brain barrier that functions as in the body, including blocking the entry of certain drugs. Significantly, when this blood-brain barrier came from cells in patients with Huntington's disease or Allan-Herndon-Dudley syndrome, a rare conbad neurological disorder, the barrier functioned in the same way as in patients with of these diseases.

While scientists had previously created blood-brain barriers to the outside of the body, this study advanced science by using induced pluripotent stem cells to create a functional blood-brain barrier, in a microarray. organ, which exhibited a characteristic defect of the patient's disease. .

The results of the study open a promising avenue for precision medicine, said Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors, Institute of Regenerative Medicine. "The ability to use a patient-specific multicellular model of a blood-brain barrier on a chip represents a new standard for the development of a predictive and personalized medicine," he said. declared. Svendsen, professor of medicine and biomedical sciences, was the principal author of the study.

The research combined the innovative stem cell science of investigators at Cedars-Sinai in Los Angeles with the advanced Organs-on-Chips technology from Emulate, Inc. in Boston. The emulate human emulation system recreates the microenvironment necessary for cells to exhibit an unprecedented level of biological function and behave as they are in the human body. The system consists of instruments, software applications and organ chips, the size of an AA battery, endowed with tiny fluidic channels lined with tens of thousands of living human cells .

The co-first authors of the study are Gad Vatine, PhD, from Ben Gurion University of the Negev in Beer Sheva, Israel, former postdoctoral fellow at Cedars-Sinai; Riccardo Barrile, PhD, of Emulate, a former postdoctoral fellow at Cedars-Sinai; and Michael Workman, Ph.D. student at the Cedars-Sinai School of Biomedical Sciences.

The research is part of several collaborative projects between Cedars-Sinai and Emulate, Inc. which, in February 2018, announced the creation of a joint Patient-on-a-Chip program to predict which treatments would be the most effective. more efficient given the genetic constitution of the patient and its properties. variant of the disease. The program is an initiative of Cedars-Sinai Precision Health, whose goal is to stimulate the development of the latest technologies and the best research, badociated with best clinical practices, to rapidly enable a new era of personalized health.

Disclosure: Cedars-Sinai holds a minority interest in Emulate, Inc. A senior executive of Cedars-Sinai sits on the Emulate Board of Directors. Emulate has not provided any financial support for this research. Six of the study's authors are employees and shareholders of Emulate.

Funding: The research reported in this publication was funded by the National Institute of Neurological Disorders and Stroke and the National Center for the Advancement of Translational Sciences of the National Institutes of Health, under the n Family Foundation and Israeli Foundation of Science.

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