Behavioral recovery following intrastriatal implantation of microencapsulated
PC12 cells.
Exp Neurol, 113 (3):
322-9 (1991)Abstract
The motor deficits associated with Parkinson's disease may be ameliorated
by intrastriatal placement of dopamine-secreting cells in a polymer
capsule. Water soluble polyelectrolytes were utilized for membrane
encapsulation of dopamine-secreting PC12 cells. Membrane permeability
studies revealed exclusion of radiolabeled 69,000 Da albumin, whereas
30,000 Da carbonic anhydrase was able to cross the membrane. No cytolytic
activity was observed following incubation of the encapsulated PC12
cells with PC12 cell-directed antiserum and fresh complement. In
vitro, dopamine release and the surface area of intact cells per
microcapsule, reached a plateau at 4 weeks that was maintained for
at least 12 weeks. Viable PC12 cells were observed in microcapsules
implanted for 4 and 8 weeks in nonlesioned guinea pig striata. The
behavioral effect of intrastriatal dopamine release from microencapsulated
PC12 cells was evaluated in the 6-hydroxydopamine unilaterally lesioned
rat model. From 1 to 4 weeks postimplantation a significant reduction
in rotation behavior under apomorphine challenge was observed with
PC12 cell-loaded microcapsules as compared to empty microcapsules.
Tyrosine hydroxylase immunopositive PC12 cells were observed 4 weeks
postimplantation in all animals exhibiting a reduction in turning
behavior. Implantation of polymer-encapsulated cells may provide
a means for long-term delivery of neurotransmitters and growth factors
to the nervous system.