Generation Of Choroid Plexus Epithelial Cells From Human Embryonic Stem Cells
Based on the ability to expand human ESCs to large numbers in culture, the invention should enable the subsequent production of large numbers of CPe cells for a variety of downstream applications.
Proposed uses include efficacy testing of human CPe cells as therapeutics in animal models of neurodegenerative diseases, genetic engineering of CPe cells to produce large amounts of secretory proteins, and drug screens using cultured CPe cells to identify compounds that can cross the blood-CSF barrier.
Choroid plexus epithelial (CPe) cells are a relatively understudied cell type in the nervous system with untapped clinical potential. These cells are the primary cells comprising the choroid plexus, the tissue that produces the cerebrospinal fluid (CSF) that bathes and nourishes the human brain. The CPe cells also form a physical barrier (“blood-CSF barrier”) and has important adsorptive functions that protect the brain from toxins. Atrophy and other defects in CPe cells have been implicated in human neurodegenerative diseases, particularly Alzheimer’s Disease, and choroid plexus transplant studies have shown benefit in animal models of some of these diseases. The ability to generate large number of CPe cells in culture, which is not currently possible, should therefore enable a number of novel clinical applications. In published animal model studies, whole choroid plexus dissected from donor rodents have been used as transplant sources. A human source for transplantable CPe cells has not previously been available. In addition, unlike some other epithelia in the human body, the CPe is not highly proliferative and does not turnover significantly, which makes expansion of CPe cells from the endogenous choroid plexus in culture less feasible. The process developed at the University of California involves the generation of human CPe cells from human embryonic stem cells (ESCs). Certain nervous system cells are first generated from human ESCs using previously-published protocols. These nervous system cells are then cultured with an inducer of CPe cell fate. CPe identity in culture is then assessed and confirmed using a variety of morphologic and molecular parameters (histology, immunocytochemistry, real-time qRT-PCR, and electron microscopy).
Patent Number: US8748176B2
Application Number: US13370054A
Inventor: Monuki, Edwin S. | Watanabe, Momoko
Priority Date: 9 Feb 2011
Priority Number: US8748176B2
Application Date: 9 Feb 2012
Publication Date: 10 Jun 2014
IPC Current: C12N0005071 | C12N000500 | C12N000502 | C12N000507
US Class: 435366 | 435354 | 435377 | 435384
Assignee Applicant: The Regents of the University of California
Title: Generation of choroid plexus epithelial cells from human embryonic stem cells
Usefulness: Generation of choroid plexus epithelial cells from human embryonic stem cells
Summary: The method (M1) is useful for inducing CPECs which is useful for treating neurogenic disease, preferably Alzheimer's disease in animal, preferably human. The method (M2) is useful for engrafting endogenous CP epithelium with CPECs (all claimed).
Novelty: Inducing choroid plexus epithelial cells used for treating neurogenic disease preferably Alzheimer's disease, by adding bone morphogenetic protein and members of transforming growth factor-beta superfamily to embryonic stem cells
Biomedical
Medical Imaging
Tech ID/UC Case 21453/2010-316-0 Related Cases 2010-316-0
USA
