Behavioral recovery following intrastriatal implantation of microencapsulated PC12 cells.
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.
Section of Artificial Organs, Brown University, Providence, Rhode Island 02912.
S R
SR
Winn
P A
PA
Tresco
B
B
Zielinski
L A
LA
Greene
C B
CB
Jaeger
P
P
Aebischer
D000818:Animals; D001522:Behavior, Animal; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D008297:Male; D016716:PC12 Cells / Q000637:transplantation*; D051381:Rats; D011919:Rats, Inbred Strains
D004298:Dopamine