Polymer-Encapsulated PC-12 Cells Demonstrate High-Affinity Uptake of Dopamine in Vitro and ¹⁸F-DOPA Uptake and Metabolism after Intracerebral Implantation in Nonhuman Primates

Abstract

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10(8) fmol/min x 10(6) cells, and that this uptake can be specifically blocked 88% by the addition of 10nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18-F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

PC 12 Pheochromocytoma Cell Response to Super High Frequency Terahertz Radiation from Synchrotron Source

“…Whether this is indeed the case, however, remains a subject of debate as studies are limited by the scarcity of efficient THz generating sources and sensitive detectors [6]. For example, human dermal fibroblasts exposed to continuous THz radiation from an optically pumped molecular gas THz laser source (2.52 THz, 227 mW/cm 2 ) for up to 80 min were shown to be 90% viable [10,11,12]. When exposed to the narrow-band THz radiation (2.3 THz, 1.4 W/cm 2 ), human embryonic stem cells (hESCs) showed no structural chromosomal aberrations or difference in cell morphology when compared to the untreated control, and only some minor upregulations of mitochondria-related genes were reported [1].…”

Intracompartmental Delivery of CNTF as Therapy for Huntingtons Disease and Retinitis Pigmentosa

“…Spontaneous and evoked release of dopamine can be detected from capsules maintained both in vitro, and following explantation from the CNS. Both rodent microdialysis and positron emission tomography (PET) studies in primates have confirmed that encapsulated PC12 cells continue to produce L-dopa / dopamine in situ [Tresco et al, 1992;Subramanian et al, 1997]. …”

Synthesis, Biodistribution, and Primate Imaging of Fluorine-18 Labeled 2β-Carbo-1‘-fluoro-2-propoxy-3β-(4-chlorophenyl)tropanes. Ligands for the Imaging of Dopamine Transporters by Positron Emission Tomography

“…A left intracarotid infusion of MPTP was performed on the female rhesus monkey by a previously reported method, 30 several weeks prior to the PET study.…”