Abstract
Cell therapy with polymer capsules has been developed for central nervous system diseases [1], such as Parkinson’s disease [2], amyotrophic lateral sclerosis [3] and cancer pain [4,5]. The use of encapsulated cells has great potential advantages, including constant delivery of the products and avoidance of rejection by the host immune system. An ability to control the expression levels of products in cell transplantation therapy would provide further significant advantages. Ideally, transfected genes in the implanted grafts should be regulated intrinsically, leading to delivery of neuropeptides or transmitters on demand. A practical alternative might be to control gene expression of transfected cells exogenously. Several attempts to control gene expression in such cells have been reported, i.e., regulation by steroid hormones [6], isopropyl [3-D-thiogalactoside [7], and heavy metals [8], but most of these substances may induce serious side effects in vivo.
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References
Rosenberg MB, Friedmann T, Robertson RC, et al (1988) Grafting genetically modified cells to the damaged brain: Restorative effects of NGF expression. Science 242:1575–1578
Shingo T, Date I, Yoshida H, et al (2002) Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNF-producing cells in a rat model of Parkinson’s disease. J Neurosci Res 69:946–954
Zurn AD, Henry H, Schluep M, et al (2000) Evaluation of an intrathecal immune response in amyotrophic lateral sclerosis patients implanted with encapsulated genetically engineered xenogeneic cells. Cell Transplant 9:471–478
Sagen J, Wang H, Tresco P, et al (1998) Transplants of immunologically isolated xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances. J Neurosci 13:2415–2423
Saitoh Y, Taki T, Arita N, et al (1995) Analgesia induced by transplantation of encapsulated tumor cells secreting beta-endorphin. J Neurosurg 82:630–634
Braselmann S, Graninger P, Busslinger M (1993) A selective transcriptional induction system for mammalian cells based on Gal4-estrogen receptor fusion proteins. Proc Natl Acad Sci U.S.A. 90:1657–1661
Bairn SB, Labow MA, Levine AJ, et al (1991) A chimeric mammalian transactivator based on the lac repressor that is regulated by temperature and isopropyl beta-D-thiogalactopyranoside. Proc Natl Acad Sci U.S.A. 88:5072–5076
Mayo KE, Warren R, Palmiter RD (1982) The mouse metallothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. Cell 29:99–108
Gossen M, Freundlieb S, Bender G, et al (1995) Transcriptional activation by tetracyclines in mammalian cells. Sicence 268:1766–1769
Noel G, Zollinger L, Laliberte F, et al (1989) Targeting and processing of pro-opiomelanocortin in neuronal cell lines. J Neurochem 52:1050–1057
Hagihara Y, Saitoh Y, Arita N, et al (1999) Long-term functional assessment of encapsulated cells transfected with Tet-On system. Cell Transplant 8:431–434
Saitoh Y, Eguchi Y, Hagihara Y, et al (1998) Dose-dependent doxycycline-mediated adrenocorticotropic hormone secretion from encapsulated Tet-On proopiome-lanocortin Neuro2A cells in the subarachnoid space. Hum Gene Ther 9:997–1002
Ghaddar G, Ruchon AF, Carpentier M, et al (2000) Molecular cloning and biochemical characterization of a new mouse testis soluble-zinc-metallopeptidase of the neprilysin family. Biochem J 347:419–429
Saitoh Y, Eguchi Y, Nakahira R, et al (2004) Controlled secretion of β-endorphin from human embryonic kidney cells carrying a Tet-on-β-endorphin fusion gene. Brain Res Mol Brain Res 121:151–155
Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U.S.A. 89:5547–5551
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© 2006 Springer-Verlag Tokyo
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Saitoh, Y., Eguchi, Y., Yoshimine, T., Boileau, G. (2006). Controlled Secretion of β-endorphin from Human Embryonic Kidney Cells Carrying a Tet-on-NL1-β-endorphin Fusion Gene: Gene Therapy of Pain. In: Kanno, T., Kato, Y. (eds) Minimally Invasive Neurosurgery and Multidisciplinary Neurotraumatology. Springer, Tokyo. https://doi.org/10.1007/4-431-28576-8_18
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DOI: https://doi.org/10.1007/4-431-28576-8_18
Publisher Name: Springer, Tokyo
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