Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease: a preclinical primate study

Abstract

Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present study was performed using nonhuman primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials. Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell—grafted groups. Due to the immunological reaction of the host brain no unencapsulated PC12 cells remained in the grafted area 8 weeks after transplantation. On the contrary, encapsulated PC12 cells retrieved from the host brain continued to release dopamine and levodopa even 8 weeks after implantation. The host's reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells. Conclusions. These results suggest that the transplantation of encapsulated PC12 cells could be a safe and effective treatment modality for Parkinson disease in human patients.