Cell therapy with encapsulated xenogeneic tumor cells secreting beta-endorphin for treatment of peripheral pain

Cell Transplant. 1995:4 Suppl 1:S13-7. doi: 10.1016/0963-6897(94)00072-r.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenocorticotropic Hormone / biosynthesis
  • Adrenocorticotropic Hormone / metabolism
  • Analgesia / methods*
  • Analysis of Variance
  • Animals
  • Capsules
  • Cell Line
  • Cell Transplantation*
  • Electric Stimulation
  • Hot Temperature
  • Male
  • Mice
  • Neuroblastoma
  • Pain Management*
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Transfection
  • Transplantation, Heterologous*
  • Tumor Cells, Cultured
  • beta-Endorphin / biosynthesis*
  • beta-Endorphin / metabolism

Substances

  • Capsules
  • Recombinant Proteins
  • beta-Endorphin
  • Adrenocorticotropic Hormone