Update on immunoisolation cell therapy for CNS diseases.
Delivery of potentially therapeutic drugs to the brain is hindered by the blood-brain barrier (BBB), which restricts the diffusion of drugs from the vasculature to the brain parenchyma. One means of overcoming the BBB is with cellular implants that produce and deliver therapeutic molecules. Polymer encapsulation, or immunoisolation, provides a means of overcoming the BBB to deliver therapeutic molecules directly into the CNS region of interest. Immunoisolation is based on the observation that xenogeneic cells can be protected from host rejection by encapsulating, or surrounding, them within an immunoisolatory, semipermeable membrane. Cells can be enclosed within a selective, semipermeable membrane barrier that admits oxygen and required nutrients and releases bioactive cell secretions, but restricts passage of larger cytotoxic agents from the host immune defense system. The selective membrane eliminates the need for chronic immunosuppression of the host and allows the implanted cells to be obtained from nonhuman sources. In this review, cell immunoisolation for treating CNS diseases is updated from considerations of device configurations, membrane manufacturing and characterization in preclinical models of Alzheimer's and Huntington's disease.
Emerich
D F
DF
Department of Neuroscience, Alkermes, Inc, Cambridge, MA 02139, USA.
Salzberg
H C
HC
D000544:Alzheimer Disease / Q000628:therapy; D000818:Animals; D001672:Biocompatible Materials; D001812:Blood-Brain Barrier / Q000276:immunology; D016380:Brain Tissue Transplantation; D017690:Cell Transplantation / Q000379:methods*; D002493:Central Nervous System Diseases / Q000628:therapy*; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D004339:Drug Compounding / Q000379:methods; D016332:Fetal Tissue Transplantation; D006801:Humans; D006816:Huntington Disease / Q000628:therapy; D066298:In Vitro Techniques; D008422:Materials Testing; D008567:Membranes, Artificial; D014183:Transplantation, Heterologous
D001672:Biocompatible Materials; D008567:Membranes, Artificial