Transplantation of encapsulated cells secreting human beta-endorphin in cerebro-spinal space for cancerpain

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Recently the technique of transplantation of encapsulated cells has progressed. Semipermeable membranes used for capsules allow transport of low molecular weight substances, but prevent the inward diffusion of both the humoral and cellular elements of the immune system. The proopiomelanocortin (POMC) gene transfected Neuro2A cells (mouse cell line) which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5x10^6/ml, and transplanted into the spinal CSF space from the occipito-atlantal junction of male Sprague-Dawley rats. The rats with encapsulated Neuro2A showed significantly less sensitive to pain than the control animals. Morphological study revealed that the encapsulated cells survived for a month after transplantation. However, the encapsulated Neuro2A in the CSF space of Japanese monkeys showed much worse viability than that of rats. We speculated that complement or natural antibody may penetrate the capsules and attack the xenogeneic cells. Therefore, sensi … More tised sheep red blood cells were encapsulated and incubated in 10% human serum medium, and the degree of the hemolysis was measured. The result suggested that double membrane consisted of PM30 (Amicon Co.) and K6305 (Kuraray Co.) could prohibit the penetration of complement in vitro. However, Neuro2A encapsulated in double capsules showed poor viability in the CSF space of Japanese monkeys. Now its reason is studied.In our study, it has been a little difficult to control the amount of secreted opiate. However, recently, the transcriptional activation system (Tet-On system) by tetracycline has been developed, and this system may help the control of opiate secretion. The pUHD10-3-POMC and pUHD172-1neo were co-transfectred to Neuro2A,named Neuro2A-POMC.Encapsulated Neuro2A-POMC was transplanted in rat CSF space. Doxycycline 5.0,2.0,0.5 and 0 mg were injected intraperitoneally 4 times every 6 hours. The peptides secretions were well correlated with the dose of doxycycline. Tet-On system is appliable for cell therapy in CNS sytem. Less