Cell therapy with encapsulated xenogeneic tumor cells secreting beta-endorphin for treatment of peripheral pain.
The purpose of this study was to assess whether xenogeneic tumor cells secreting beta-endorphin and immunologically isolated in polymer capsules could survive and continue to reduce pain when transplanted into the spinal cerebro-spinal fluid (CSF) space of rats. Also, a silicone container for polymer capsules was designed for the clinical application of this method of cell therapy. The mouse tumor cell lines, proopiomelanocortin gene transfected Neuro2A which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5 x 10(6)/mL, and transplanted into the spinal CSF space from the occipito-atlantal junction of male Sprague-Dawley rats. Three analgesiometric tests--the tail pinch test, the hot plate test, and electrical stimulation test--showed that the rats with encapsulated Neuro2A (n = 6) were significantly less sensitive to pain after transplantation than control animals (n = 8). The analgesia induced by the encapsulated cells secreting beta-endorphin was attenuated by the opiate antagonist naloxone. Morphological study revealed that the encapsulated cells survived for 1 mo after transplantation into the CSF space. An in vitro experiment on cultured capsules (3 cm long) with a silicone container (Kaneka Medics Co) showed that the encapsulated Neuro2A (5 x 10(6) mL) could secrete peptides for 1 mo. The results of this study indicate that immunologically isolated xenogeneic tumor cells can secrete opiate in the CSF space, and that a silicone container may help the application of this method to the treatment of cancer pain.
Saitoh
Y
Y
Department of Neurosurgery, Osaka University Medical School, Japan.
Taki
T
T
Arita
N
N
Ohnishi
T
T
Hayakawa
T
T
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis / Q000378:metabolism; D000698:Analgesia / Q000379:methods*; D000704:Analysis of Variance; D000818:Animals; D002214:Capsules; D002460:Cell Line; D017690:Cell Transplantation; D004558:Electric Stimulation; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009447:Neuroblastoma; D059408:Pain Management; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001615:beta-Endorphin / Q000096:biosynthesis* / Q000378:metabolism
D002214:Capsules; D011994:Recombinant Proteins; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone