New Method Converts Embryonic Stem Cells into Cells Critical to Spinal Fluid Development and Maintenance

Neurological disease researchers have developed a technique for generating choroid plexus epithelial cells (CPECs) from neuroepithelial progenitors derived from embryonic stem cells.

CPECs are essential to the developmental and maintenance of the CSF and blood–CSF barrier they produce, and CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer's disease. Transplant studies have provided proof-of-concept for CPEC-based therapies, but development of such therapies has been hindered by the inability to expand or generate CPECs in culture.

In the current study investigators at the University of California, Irvine (USA; www.uci.edu) searched for the appropriate growth factors that would induce mouse or human embryonic stem cells to differentiate into functional CPECs. In particular, they looked at the role of bone morphogenetic protein (BMP) signaling, which was known to be required for the differentiation of CPECs from preneurogenic neuroepithelial cells during embryonic development.

Results published in the November 7, 2012, online edition of the Journal of Neuroscience revealed that neural progenitor cells could be derived from mouse or human embryonic stem cells. Exposure of these cells to the protein BMP4 was sufficient to induce them to mature into CPECs. Analysis of these cells showed that in addition to molecular, cellular, and ultrastructural criteria, the derived CPECs (dCPECs) demonstrated functionality that was indistinguishable from primary CPECs, including self-assembly into secretory vesicles and integration into endogenous choroid plexus epithelium.

“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 senior author Dr. Edwin Monuki, associate professor of pathology and laboratory medicine and developmental and cell biology at the University of California, Irvine.

Dr. Monuki said, “The next steps are to develop an effective drug screening system and to conduct proof-of-concept studies to see how these CPECs affect the brain in mouse models of Huntington’s, Alzheimer’s, and pediatric diseases.”

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University of California, Irvine