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

Research Project

Project/Area Number 07557360
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section試験
Research Field Cerebral neurosurgery
Research InstitutionOsaka University

Principal Investigator

SAITOH Youichi  Osaka Univ., Dept.of Neurosurg., Assistant Professor, 医学部, 助手 (20252661)

Co-Investigator(Kenkyū-buntansha) NATSUME Toru  Nippon Meat Packers Inc., Research & Development Center, Researcher, 中央研究所, 研究員
MUKAI Tsunehiro  National Cardiovascular, Dept.of Bioscience, Director Center Research Inst., バイオサイエンス部, 部長 (40108741)
IWATA Hiroo  Kyoto Univ., Research Centerfor, Associate Professor Biomedical Engineering, 生体医療工学センター, 助教授 (30160120)
OHNISHI Takanori  Osaka Univ., Dept.of Neurosurg., Assistant Professor, 医学部, 助手 (70233210)
HAYAKAWA Toru  Osaka Univ., Dept.of Neurosurg., Professor, 医学部, 教授 (20135700)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordspain / xenograft / beta-endorphin / polymer capsule
Research Abstract

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

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Y. Hagiwara, Y. Saitoh et al: "Transplantation of the xenogeneic cells secreting β-endorphin for pain treatment : Analysis of the permeability of complements through polymer capsules." Cell Trensplantation. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岡成光、斎藤洋一他: "Pergolide mesilateが著効したしたprolactinomaの一例" ホルモンと臨床 間脳下垂体腫瘍VI. 45. 112-115 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S M Ekramullarh, Y Saitoh et al: "The correlation of Ki-67 staiing indices with tumour doubling times in recurrent non-functionig pituitary adenomas" Acta Neurochirurgica. 138. 1449-145. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A C Gore, Y Saitoh et al: "Effects of adrenal medulla transplantation into the third ventricle on the onset of puberty in femalc rhesus monkeys." Experimental Neurology. 140. 172-183 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T Uchiyama, Y Saitoh et al: "The implant of Schwann cells facilitates the regeneration of crush-injured facial nerve." Restorative Neurology Neuroscience. 9. 54 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y. Saitoh et al: "Year Book of Endocrinology" Mosby-Year Book, Inc., 2 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "Analgesia induced by trasplantation of encapsulated tumor cells secreting beta-endorphin" J Neurosurg. 82. 630-634 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "Cell therapy with encapsulated xenogenic tumor cells secreting beta-endorphin for treatment of peripheral pain" Cell Transplantation. 4 (supple 1). S13-17 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.M Ekramullarh et al: "Effects of bromocriptine on staining indices of Ki-67 and proliferating cell nuclear antigen, and nucleolar organizer region number in pituitary adenomas" Neurol Med Chir (Tokyo). 35. 221-226 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "Transplantation of the fetal olfactory placode restore reproductive cycles in female rhesus monkeys bearing lesions in the medial basal hypothalamus" Endocrinology. 136. 2760-2769 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "Analgesia induced by transplantation of encapsulated tumor cells secreting beta-endorphin" Analgesic Digest. 2. 18-21 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "Protection of the ageing in endocrine organs with bifemelane hydrochloride" Rest Neurol Neurosci. 9. 47 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "The implant of Schwann cells facilitates the regeneration of crush-injured facial nerve" Rest Neurol Neurosci. 9. 54 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Izumoto et al: "Homozygous deletions of p16^<INK4A>/MTS1 and p15^<INK4B>/MTS2 genes in glioma cells and primary glioma tissues" Cancer Letters. 97. 241-247 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Higuchi et al: "Leptomeningeal dissemination of malignant glioma : immunohistochemical analysis of tenascin and glial fibrillary acidic protein" Clin Neuropathol. 14. 223-227 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Iwata et al: "Does immunoisolation need to prevent the passage of antibodies and complements?" Transplant Proceed. 27. 3224-3226 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Yamaoka et al: "Cloning and mapping of the U2af1-rs2 gene with a high transmission distortion in interspecific backcross progeny" Genomics. 27. 337-340 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Hatada et al: "Allele-specific methylation and expression of an imprinted U2sf1-rs1 (SP2) gene" Nuc Acid Res. 23. 36-41 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Hiraga et al: "Transformation of type 1 astrocytes with N-Ethyl-N-Nitrosourea : Establishment of an in vitro system and the role of the p53 gene" Glia. 13. 51-63 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Hidaka et al: "The MEF2B homologue differentially expressed in mouse embryonal carcinoma cells" Biochem Biophy Res Comm. 213. 555-560 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.C Gore et al: "Effects of adrenal medulla transplantation into the third ventricle on the onset of puberty in female rhesus monkeys" Exp Neurol. 140. 172-183 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S M Ekramullarh et al: "The correlation of Ki-67 staiing indices with tumour doubling times in recurrent non-functionig pituitary adenomas" Acta Neurochir. 138. 1449-1455 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: "Transplantation of the xenogeneic cells secreting beta-endorphin for pain treatment : Additional genetic engineering" Rest Neurol Neurosci. 10. 182-183 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Hatada et al: "An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome" Nature Genetics. 14. 171-173 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] W.J.Wang et al: "Efficacy of microencapsulation of a pancreatic B-cell-line (MIN6) in an agarose/PSSa microbead as a bioartificial pancreas" Transplantation Proceed. 28. 1094-1096 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Hayashi et al: "Prolongation of survival of a xenografted bioartificial pancreas with a mesh-reinforced polyvinyl alcohol hydrogel bag employing a B-cell line (MIN6)" Transplantation Proceed. 28. 1097-1098 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Inoue et al: "Pig-to-rat xenotransplantation with mesh-reinforced polyvinyl alcohol bag : Efficacy of agarose gel" Transplantation Proceed. 28. 1422-1423 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Hayashi et al: "Long survival of xenografted bioartificial pancreas with a mesh-reinforced polyvinyl alcohol hydrogel bag employing a B-cell line (MIN6)" Transplantation Proceed. 28. 1428-1429 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Hiraga et al: "Establishement of spontaneously immortalized rat type 1 astroglial cell lines : The role of p53 in astroglial carcinogenesis" Glia. 18. 185-199 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Taki et al: "Antisense inhibition of the RAD51 enhaces radiosensitivity" Biochem Biophys Res Comm. 223. 434-438 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Izumoto et al: "Gene expression of Neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 glioma invasion" Cancer Research. 56. 1440-1444 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamamoto et al: "Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrinalpha6 subunit expression" Int J Cancer. 65. 519-524 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Hagiwara et al: "Transplantation of the xenogeneic cells secreting beta-endorphin for pain treatment : Analysis of the permeability of complements through polymer capsules" Cell Transplantation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Saitoh et al: Year Book of Endocrinology, "Transplantation of the fetal olfactory placode restore reproductive cycles in female rhesus monkeys bearing lesions in the medial basal hypothalamus". 24-25 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Hagiwara,Y.Saitoh et al.: "Transplantation of the xenogeneic cells secreting β-endorphin for pain treatment:Analysis of the pemeability of complements through polymer capsules." Cell Transplantation. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岡成光、齋藤洋一他: "Pergolide mesilateが著効したしたprolactinomaの一例" ホルモンと臨床 間脳下垂体腫瘍VI. 45. 112-115 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] S M Ekramullarh,Y Saitoh et al: "The correlation of Ki-67 staiing indices with tumour doubling times in recurrent non-functionig pituitary adenomas" Acta Neurochirurgica. 138. 1449-1455 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A C Gore,Y Saitoh et al.: "Effects of adrenal medulla transplantation into the third ventricle on the onset of puberty in female rhesus monkeys." Experimental Neurology. 140. 172-183 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T Uchiyama,Y Saitoh et al: "The implant of Schwann cells facilitates the regeneration of crush-injured facial nerve." Restorative Neurology Neuroscience. 9. 54 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Saitoh et al: "Year Book of Endocrinology" Mosby-Year Book,Inc., 2 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Saitoh et al: "Analgesia induced by transplantation of encapsulated tumor cells secreting β-endorphin" J Neurosurg. 82. 630-634 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Saitoh et al: "Cell therapy with encapsulated xenogeneic tumor cells secreting β-endorphin for treatment of peripheral pain" Cell Transplantation. 4(supplel). S13-17 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Saitoh et al: "Transplantation of the fetal olfactory placode restore reproductive cycles in female rhesus monkeys bearing lesions in the medial basal hypothalamus." Endocrinology. 136. 2760-2769 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Saitoh et al: "Analgesia induced by transplantation of encapsulated tumor cells secreting β-endorphin" Analgesic Digest. 2. 18-21 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Saitoh et al: "Protection of the ageing in endocrine organs with bifemelane hydrochloride" Rest Neurol Neurosci. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Saitoh et al: "The implant of Schwann cells facilitates the regeneration of crush-injured facial nerve." Rest Neurol Neurosci. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Saitoh et al: "YEAR BOOK OF PAIN" Analgesia induced by transplantation of encapsulated tumor cells secreting β-endorphin, (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 齋藤洋一 他: "機能的脳神経外科" 末梢性疼痛に対する遺伝子導入β-endorphin産生細胞含有polymer capsule髄腔内移植, 7 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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