A rich network of blood vessels located in the brain, are responsible for the
production of cerebrospinal fluid (CSF), the fluid which surrounds and cushions
the brain and spinal cord. The choroid plexus and the arachnoid membrane act
together at the barriers between the blood and CSF.
The choroid plexus not only forms the CSF but also actively regulates its'
concentration of molecules. It is highly vascularized with cauliflower-like masses
of pia tissue that flow into pockets of ependymal cells. Most of the choroid plexus is
distributed throughout the fourth ventricle near the base of the brain and in the
lateral ventricles inside the right and left cerebral hemispheres.
New Cell Type Developed in Hope of Treating Alzheimer’s and Other Brain Diseases
UC Irvine researchers have created a new stem cell-derived cell type with unique promise for treating neurodegenerative diseases such as Alzheimer’s. The discovery accelerates efforts at the Sue & Bill Gross Stem Cell Research Center
Dr. Edwin Monuki of the University of California, Irvine (UCI) in the Sue & Bill Gross Stem Cell Research Center, along with developmental & cell biology graduate student Momoko Watanabe and colleagues developed these cells choroid plexus epithelial cells (CPECs) from existing mouse and human embryonic stem cell lines.
CPECs are critical for proper functioning of the choroid plexus, the tissue in the brain that produces cerebrospinal fluid (CSF). Among their various roles, CPECs make CSF and remove metabolic waste and foreign substances from the fluid and brain.
In neurodegenerative diseases, the choroid plexus
and choroid plexus epithelial cells (CPECs) age
prematurely, resulting in reduced cerebrospinal
fluid (CSF) formation and a decreased ability
to flush out debris such as the hallmark
plaque-forming proteins of Alzheimer’s.
Although transplant studies have provided proof
of concept for CPEC-based therapies, such therapies
have been held back by the inability to expand
or generate CPECs in culture.
“Our method is promising, because for the first time we can use stem cells to create large amounts of these epithelial cells, which could be utilized in different ways to treat neurodegenerative diseases,” said Monuki, an associate professor of pathology & laboratory medicine and developmental & cell biology at UCI.
The study appears in today’s issue of The Journal of Neuroscience.
To create the new cells, Monuki and his colleagues
coaxed embryonic stem cells to differentiate into
immature neural stem cells. They then developed
the immature cells into CPECs capable of being
delivered to a patient’s choroid plexus.
These cells could be part of neurodegenerative disease treatments in at least three ways, Monuki says:
First, they’re able to increase the production of CSF
In order to help flush out plaque-causing proteins
from brain tissue and limit disease progression.
Second, CPEC “superpumps” could be designed to
transport high levels of therapeutic compounds to
the CSF, brain and spinal cord.
Third, CPEC cells can be used to screen and optimize
drugs that improve choroid plexus function.
Monuki said the next steps are to develop an effective drug screening system and to conduct proof-of-concept studies to see how CPECs affect the brain in mouse models of Huntington’s, Alzheimer’s and pediatric brain diseases.
Young-Jin Kang, Sanket Meghpara, Kimbley Lau, Chi-Yeh Chung and Jaymin Kathiriya of UCI and Anna-Katerina Hadjantonakis of the Sloan-Kettering Institute in New York contributed to the study, which received support from the National Institutes of Health (grant NS064587), the California Institute for Regenerative Medicine, UCI’s Institute for Clinical & Translational Science and UCI’s Alzheimer’s Disease Research Center.
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