Macroencapsulation of dopamine-secreting cells by coextrusion with an organic polymer solution

Abstract

A new method of coextruding living cells in the core of a forming hollow fibre is described. PC12 cells, an immortalized cell line which secretes large amounts of dopamine, and dissociated bovine adrenal chromaffin cells, a non-dividing cell type which also secretes dopamine, were coextruded by a dry-jet wet spinning technique through a double-lumen spinneret from a 15% weight by volume solution of poly(acrylonitrile vinyl chloride) in either dimethylsulphoxide (DMSO), dimethylacetamide (DMAC) or dimethylformamide (DMF). Closure of the fibre was achieved by mounting polytetrafluoroethylene tubes on a rotating coaxial wheel system which squeezed the forming hollow fibre at regular intervals. Spontaneous and potassium-stimulated release of catecholamines from the macrocapsules were quantified under static conditions by ion-pair reverse-phase high-performance liquid chromatography equipped with electrochemical detection at 2, 4 and 6 wk. At all time periods, coextruded macrocapsules with either PC12 cells or adrenal chromaffin cells released dopamine under either unstimulated or stimulated conditions. An increase over time in dopamine release was observed from PC12 cell coextruded macrocapsules with observable difference between capsules extruded with DMSO, DMAC or DMF as solvents. Well-preserved PC12 cells and adrenal chromaffin cells were present in coextruded macrocapsules with no observable difference between capsules extruded with DMSO, DMAC or DMF as inocuity of macroencapsulation by coextrusion from an organic polymer solution. Owing to the particular fluid dynamics of this technique, minimal potentially toxic cell-solvent contact occurs allowing the use of a wider range of water-insoluble polymeric systems. The ability of encapsulated PC12 cells and adrenal chromaffin cells to release spontaneously dopamine over time also suggests that polymer encapsulation may provide an alternative to the transplantation of dopamine-secreting cells in the treatment of Parkinson's disease.