HEMA/MMMA microcapsule implants in hemiparkinsonian rat brain: biocompatibility assessment using [3H]PK11195 as a marker for gliosis.

Abstract

Microencapsulation of dopamine-secreting cells in biocompatible, semi-permeable polymer membranes has been proposed as an alternative strategy for dopamine replacement for Parkinson's disease. In order to assess the viability of this proposal, dopamine-secreting PC12 cells were immunoisolated via microencapsulation in a 75:25 2-hydroxyethyl methacrylate/methyl methacrylate (HEMA/MMA) copolymer. A submerged nozzle-liquid jet method was used to produce small diameter (400 microm) microcapsules, which were stereotaxically implanted in the denervated striatum of hemi-Parkinsonian rats. A 96% survival rate was associated with the implantation surgery and no deleterious side effects were apparent. Light microscopy revealed good biocompatibility between the HEMA/MMA copolymer and the host brain, as evidenced by the absence of gross tissue damage at the neuronal tissue/capsule interface. Autoradiographic analyses using [3H]PK11195 as marker for reactive astrocytes revealed a moderate inflammatory response, confined to the immediate vicinity of the injection tract. Quantitative analyses indicated that the local tissue response did not differ significantly between brains implanted with PC12-containing capsules and those implanted with vehicle-containing capsules. Taken together, these results support the biocompatibility of HEMA/MMA copolymer as well as the feasibility and safety of stereotaxic implantation of microcapsules.