A cell encapsulation device for studying soluble factor release from cells transplanted in the rat brain.

The transplantation of a variety of naturally occurring and genetically modified cell types has been shown to be an effective experimental method to achieve sustained delivery of therapeutic molecules to specific target areas in the brain. To acquire a better understanding of dosing, implant mechanism of action, and how certain cell types affect remodeling of central nervous system (CNS) tissue, a refillable cell encapsulation device was developed for introducing cells into the brain while keeping them physically isolated from contact with brain tissue with a semipermeable membrane. The stereotactically placed device consists of a hollow fiber membrane (HFM), a polyurethane grommet with watertight cap that snaps into a precisely drilled hole in the rat skull, and a removable cell-containing insert. The cell-containing insert can be introduced or removed in a time-dependent manner to study the influence of soluble factors released from transplanted cells. The study describes the device design and validates its utility using a well-established cell transplantation model of Parkinson's disease.

Hollow fiber membrane diffusive permeability regulates encapsulated cell line biomass, proliferation, and small molecule release.

Using histological and HPLC methods, we examined the influence of hollow fiber membrane transport properties on encapsulated PC12 cell biomass, proliferation and the release of dopamine over 4 weeks in culture. Our data indicated that encapsulated cell biomass, the number of proliferating cells, and the quantity of dopamine released increased as a function of increasing hollow fiber encapsulation membrane diffusive permeability. Overall the percentage of viable cells and the biomass architecture, however, was not significantly affected by differences in membrane transport. When compared to membrane sieving properties, membrane diffusive transport and membrane hydraulic permeability were better indicators of biomass size, proliferating cell number, and dopamine release from encapsulated cells. Studies examining the sustained release of DA from membranes of differing permeability suggest that membrane diffusive permeability can be used to regulate the quantity of small molecules released per unit time at steady state, and should be considered when dosing is an important determinant of implant efficacy.