期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 67-68, 期 -, 页码 131-141出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2013.07.008
关键词
Polymer encapsulation; Cell transplantation; Neurodegeneration
Delivering therapeutic molecules, including trophic factor proteins, across the blood brain barrier to the brain parenchyma to treat chronic neurodegenerative diseases remains one of the great challenges in biology. To be effective, delivery needs to occur in a long-term and stable manner at sufficient quantities directly to the target region in a manner that is selective but yet covers enough of the target site to be efficacious. One promising approach uses cellular implants that produce and deliver therapeutic molecules directly to the brain region of interest. Implanted cells can be precisely positioned into the desired region and can be protected from host immunological attack by encapsulating them and by surrounding them within an immunoisolatory, semipermeable capsule. In this approach, cells are enclosed within a semiporous capsule with a perm selective membrane barrier that admits oxygen and required nutrients and releases bioactive cell secretions while restricting passage of larger cytotoxic agents from the host immune defense system. Recent advances in human cell line development have increased the levels of secreted therapeutic molecules from encapsulated cells, and membrane extrusion techniques have led to the first ever clinical demonstrations of long-term survival and function of encapsulated cells in the brain parenchyma. As such, cell encapsulation is capable of providing a targeted, continuous, de novo synthesized source of very high levels of therapeutic molecules that can be distributed over significant portions of the brain. (C) 2013 Elsevier B.V. All rights reserved.
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