POLYMER SCIENCE FOR MACROENCAPSULATION OF CELLS FOR CENTRAL-NERVOUS-SYSTEM TRANSPLANTATION

The goal of encapsulated cell therapy research is to develop implants containing living xenogeneic cells to treat serious and disabling huma n conditions. The enabling concept is straightforward: cells or small clusters of tissue are surrounded by a selective membrane barrier whic h admits oxygen and required metabolites, releases bioactive cell secr etions but restricts the transport of the larger cytotoxic agents of t he body's immune defense system. Use of a selective membrane both elim inates the need for chronic immunosuppression in the host and allows c ells to be obtained from non-human sources, thus avoiding the cell-sou rcing constraints which have limited the clinical application of gener al successful investigative trials of unencapsulated cell transplantat ion for chronic pain, Parkinson's disease, and type I diabetes. Target applications for encapsulated cell therapy include these same disorde rs as well as other disabilities caused by loss of secretory cell func tion which cannot be adequately treated by current organ transplantati on or drug therapies and conditions potentially capable of responding to local sustained delivery of growth factors and other biologic respo nse modifiers. Several types of device configurations are possible. He re we focus on easily retrieved, non-vascularized, macrocapsules. Such devices have four basic components: a hollow fiber or flat sheet memb rane (usually thermoplastic based), cells (primary or dividing), and e xtracellular matrix (natural or synthetic) to promote cell viability a nd function, and other device components such as seals, tethers and ra dio-opaque markers. Choice of membrane and extracellular matrix polyme rs as well as issues surrounding implantation and biocompatibility eva luation are complex, inter-related, and ultimately driven by implantat ion site and delivery requirements. Cross species immunoisolated cell therapy has been validated small and large animal models of chronic pa in, Parkinson's disease, and type I diabetes and is under active inves tigation by several groups in animal models of Huntington's, Hemophili a, Alzheimer's, ALS, and other CNS disorders.