Therapeutic potential of a polymer-encapsulated L-DOPA and dopamine-producing cell line in rodent and primate models of Parkinson's disease.
Encapsulation of cells within polymer membranes prior to transplantation provides a novel means of achieving continuous, site-specific delivery of therapeutic molecules to the CNS. The use of encapsulated dopamine-secreting cells that can be transplanted directly into the striatum has particular appeal for the treatment of Parkinson's disease. This article provides a brief and timely review of the progress that has been made over the past decade using encapsulated PC12 cells as a means of delivering dopamine and L-DOPA to the striatum in rodent and primate models of Parkinson's disease. The polymer membranes are well tolerated and biocompatible. Encapsulated PC12 cells survive in vivo for up to 6 mo, they release dopamine into the surrounding host striatum, and they clearly improve behavioral function in both dopamine-depleted rodents and primates. Although these results are promising, fundamental issues remain concerning the extent of dopamine diffusion from the polymer membranes and the number of devices needed for behavioral improvement, and the duration and consistency of cell viability and device output. Nevertheless, this technology appears to be a promising means of avoiding many of the practical, societal, and ethical issues that have been associated with other transplantation approaches.
Lindner
M D
MD
CytoTherapeutics Inc., Lincoln, RI 02865, USA.
Emerich
D F
DF
D000818:Animals; D001709:Biotechnology; D017690:Cell Transplantation; D003342:Corpus Striatum; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage* / Q000096:biosynthesis*; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D007980:Levodopa / Q000008:administration & dosage* / Q000096:biosynthesis*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy*; D011108:Polymers; D011323:Primates; D051381:Rats
D011108:Polymers; D007980:Levodopa; D004298:Dopamine