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Application of Polymer-Encapsulated Cell Therapy for CNS Diseases

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Neural Transplantation Methods

Part of the book series: Neuromethods ((NM,volume 36))

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Abstract

A major goal of neuroscience research is to develop effective treatments for clinical disorders, including those with underlying central nervous system (CNS) dysfunction. Progressive CNS diseases are characterized by the continuous deterioration of both cognitive and motor functions, leading to prolonged periods of increasing incapacity. Among the most problematic and prevalent neurological disorders are those associated with the loss of specific populations of brain neurons. Today, approx 12 million people in the United States suffer from such neurological disorders. Estimated costs in the United States of public expenditures and secondary medical expenses for treating patients with neurological disorders exceed $400 billion annually. Expenses directly attributed to organic neurological disease account for only about 25% of that amount. Beyond monetary costs to the health care economy, however, the medical, societal, familial, and personal costs cascading from these diseases defy calculation. Despite significant advances in technology and in understanding CNS disorders, effective treatments for progressive neurological disorders remain elusive.

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References

  • Aebischer, P., Buschser, E., Joseph, J. M., Favre, J., de Tribolet, N., Lysaght, M. J., Rudnick, S. A., and Goddard, M. B. (1994a) Transplantation in humans of encapsulated xenogeneic cells without immunosuppression: a preliminary report. Transplantation 58, 1275–1277.

    Article  PubMed  CAS  Google Scholar 

  • Aebischer, P., Goddard, M., Signore, P., and Timpson, R. (1994b) Functional recovery in hemiparkinsonian primates transplanted with polymer encapsulated PC 12 cells. Exp. Neurol. 126, 1–12.

    Article  Google Scholar 

  • Aebischer, P., Schleup, M., Deglon, N., Joseph, J.-M., Hirt, L., Heyd, B., Goddard, M., Hammang, J. P., Zurn, A. D., Kato, A. C., Regli F., and Baetge, E. E. (1996) Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Med. 2, 696–699.

    Article  PubMed  CAS  Google Scholar 

  • Aebischer, P., Tresco, P. A., Winn, S. R., Greene, L. A., and Jaeger, C. B. (1991a) Long-term cross-species brain transplantation of a polymer encapsulated dopamine-secreting cell line. Exp. Neurol. 111, 269–275.

    Article  PubMed  CAS  Google Scholar 

  • Aebischer, P., Wahlberg, L., Tresco, P. A., and Winn, S. R. (1991b) Macroencapsulation of dopamine-secreting cells by coextrusion with an organic polymer solution. Biomaterials 12, 50–56.

    Article  PubMed  CAS  Google Scholar 

  • Aebischer, P., Winn, S. R., and Galletti, P. (1988) Transplantation of neural tissue in polymer capsules. Brain Res. 448, 364–368.

    Article  PubMed  CAS  Google Scholar 

  • Bakay, R. A., Barrow, D. L., Fiandaca, M. S., Iuvone, P. M., Schiff, A., and Collins, D. C. (1987) Biochemical and behavioral correction of MPTP Parkinson-like syndrome by fetal cell transplantation. Ann. NY Acad. Sci. 495, 623–640.

    Article  PubMed  CAS  Google Scholar 

  • Bakay, R. A., Fiandaca, M. S., Barrow, D. L., Schiff, A., and Collins, D. C. (1985) Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced Parkinson-like syndrome in primates. Appl. Neurophysiol. 48, 358–361.

    PubMed  CAS  Google Scholar 

  • Bankiewicz, K. S., Plunkett, R. J., Jacobowitz, D. M., Porrino, L., di Porzio, U., London, W. T., Kopin, I. J., and Oldfield, E. H. (1990) Effect of fetal mesencephalon implants on primate MPTP-induced parkinsonism. Histochemical and behavioral studies. J. Neurosurg. 72, 231–244.

    Article  PubMed  CAS  Google Scholar 

  • Batchelor, P. E., Armstrong, D. M., Blaker, S. N., and Gage, F. H. (1989) Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: response to fimbria-fornix transection. J. Comp. Neurol. 284, 187–204.

    Article  PubMed  CAS  Google Scholar 

  • Beal, M. F., Kowall, N. W., Ellison, D. W., Mazurek, M. F., Swartz, K. J., and Martin, J. B. (1986) Replication of the neurochemical characteristics Huntington’s disease by quinolinic acid. Nature 321, 168–171.

    Article  PubMed  CAS  Google Scholar 

  • Beal, M. F., Kowall, N. W., Swartz, K. J., Ferranti, R. J., and Martin, J. B. (1989) Differential sparing of somatostatin-neuropeptide Y and cholinergic neurons following striatal excitotoxin lesions. Synapse 3, 38–47.

    Article  PubMed  CAS  Google Scholar 

  • Beal, M. F., Mazurek, M. F., Ellison, D. W., Swartz, K. J., McGarvey, U., Bird, E. D., and Martin, J. B. (1988) Somatostatin and neuropeptide Y concentrations in patho-logically graded cases of Huntington’s disease. Ann. Neurol. 23, 562–569.

    Article  PubMed  CAS  Google Scholar 

  • Becker, J., Robinson, T. E., Barton, P., Sintov, A., Siden, R., and Levy, R. J. (1990) Sustained behavioral recovery from unilateral nigrostriatal damage produced by the controlled release of dopamine from a silicone polymer pellet placed into the denervated striatum. Brain Res. 508, 60–64.

    Article  PubMed  CAS  Google Scholar 

  • Bellamkonda, R., Ranieri, J. P., and Aebischer, P. (1995) Laminin oligopeptide derivatized agarose gels allow three-dimensional neurite extension in vitro. J. Neuro. Sci. Res. 41, 501–509.

    Article  CAS  Google Scholar 

  • Björklund, A. and Stenevi, U. (1997) Reformation of the severed septohippocampal cholinergic pathway in the adult rat by transplanted septal neurons. Cell Tiss. Res. 185, 289–302.

    Google Scholar 

  • Björklund, A., Dunnett, S. B., Stenevi, U., Lewis, M. E., and Iversen, S. D. (1980) Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing. Brain Res. 199, 307–333.

    Article  PubMed  Google Scholar 

  • Björklund, A., Gage, F. H., Schmidt, R. H., Stenevi, U., and Dunnett, S. B. (1983b) Intracerebral grafting of neuronal cell suspensions VII. Recovery of choline acetyl-transferase activity and acetylcholine synthesis in the denervated hippocampus reinnervated by septal suspension implants. Acta Physiol. Scand. 522(Suppl), 59–66.

    Google Scholar 

  • Björklund, A., Gage, F. H., Stenevi, U., and Dunnett, S. B. (1983a) Intracerebral grafting of neuronal cell suspensions VI. Survival and growth of intrahippocampal implants of septal cell suspensions. Acta Physiol. Scand. 522(Suppl), 49–58.

    Google Scholar 

  • Björklund, A., Stenevi, U., Dunnett, S. B., and Gage, F. H. (1982) Cross-species neural grafting in a rat model of Parkinson’s disease. Nature 298, 652–654.

    Article  PubMed  Google Scholar 

  • Block, F., Kunkel, M., and Schwarz, M. (1993) Quinolinic acid lesion of the striatum induces impairment in spatial learning and motor performance in rats. Neurosci. Lett. 149, 126–128.

    Article  PubMed  CAS  Google Scholar 

  • Brauker, J. H., Carrbrendel, V. E., Martinson, L. A., Crudele, J., Johnston, W. D., and Johnson, W. C. (1995) Neovascularization of synthetic membranes directed by membrane microarchitecture. J. Biomed. Mater. Res. 29, 1517–1524.

    Article  PubMed  CAS  Google Scholar 

  • Brundin, P., Strecker, R. E., Widner, H., Clarke, D. J., Nilsson, O. G., Ã…stedt, B., Lindvall, O., and Björklund, A. (1988) Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp. Brain Res. 70, 192–208.

    PubMed  CAS  Google Scholar 

  • Buschser, E., Goddard, M., Heyd, B., Joseph, J. M., Favre, J., de Tribolet, N., Lysaght, M., and Aebischer, P. (1996) Immunoisolated xenogenic chromaffin cell therapy for chronic pain. Initial clinical experience. Anesthesiology 85, 1005–1012.

    Article  Google Scholar 

  • Cabasso, I. (1980) Hollow fiber membranes, in Encyclopaedia of Chemical Technology, vol. 12 (Kirk-Othmer, ed.), Wiley, New York, pp. 492–517.

    Google Scholar 

  • Christenson, L., Dionne, K. E., and Lysaght, M. J. (1993) Biomedical applications of immobilized cells, in Fundamentals of Animal Cell Encapsulation and Immobilization (Goosen, M. F. A., ed.), CRC, Boca Raton, pp. 7–41.

    Google Scholar 

  • Cima, L. G., Lopina, S. T., Kaufamn, M., and Merrill, E. W. (1994) Polyethylene oxide hydrogels modified with cell attachment ligands, American Society for Artificial Internal Organs (ASAIO) National Meeting, San Francisco.

    Google Scholar 

  • De Yebenes, J. G., Fahn, S., Mena, M. A., Pardo, B., and Casarejos, M. J. (1988) Intracerebroventricular infusion of dopamine and its agonists in rodents and primates: an experimental approach to the treatment of Parkinson’s disease. Trans. Am. Soc. Artif. Intern. Organs 34, 951–957.

    Google Scholar 

  • Dunn, J. C. Y., Tompkins, R. G., and Yarmush, M. L. (1991) Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol. Prog. 7, 237–245.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F., Frydel, B., McDermott, P., Krueger, P., Lavoie, M., Sanberg, P. R., and Winn, S. R. (1993a) Polymer-encapsulated PC12 cells promote recovery of motor function in aged rats. Exp. Neurol. 122, 37–47.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F. and Sanberg, P. R. (1992b) Animal models in Huntington’s disease, in Neuromethods, vol. 17, Animal Models of Neurological Disease (Boulton, A. A., Baker, G. B., and Butterworth, R. F., eds.), Humana, Totowa, NJ, pp. 65–134.

    Google Scholar 

  • Emerich, D. F., Black, B. A., Kesslak, J. P., Cotman, C. W., and Walsh, T. J. (1992a) Transplantation of fetal cholinergic neurons into the hippocampus attenuates the cognitive and neurochemical deficits induced by AF64A. Brain Res. Bull. 28, 219–226.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F., Frydel, B., Flanagan, T. R., Palmatier, M., Winn, S. R., and Christenson, L. (1993b) Transplantation of polymer encapsulated PC 12 cells: use of chitosan as an immobilization matrix. Cell Transplant. 2, 241–249.

    Google Scholar 

  • Emerich, D. F., Hammang, J. P., Baetge, E. E., and Winn, S. R. (1994a) Implantation of polymer-encapsulated human nerve growth factor-secreting fibroblasts attenuates the behavioral and neuropathological consequences of quinolinic acid injections into rodent striatum. Exp. Neurol. 130, 141–150.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F., Lindner, M. D., Winn, S. R., Chen, E.-Y., Frydel, B. R., and Kordower, J. H. (1996) Implants of encapsulated human CNTF-producing fibroblasts prevent behavioral deficits and striatal degeneration in a rodent model of Huntington’s disease. J. Neurosci. 16, 5168–5181.

    PubMed  CAS  Google Scholar 

  • Emerich, D. F., Winn, S. R., Hantraye, P. M., Peschanski, M., Chen, E.-Y., Chu, Y., McDermott, P., Baetge, E. E., and Kordower, J. H. (1997a) Protective effects of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington’s disease. Nature 386, 395–399.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F., Winn, S. R., Harper, J., Hammang, J. P., Baetge, E. E,. and Kordower, J. H. (1994b) Implants of polymer-encapsulated human NGF-secreting cells in the nonhuman primate: rescue and sprouting of degenerating cholinergic basal fore-brain neurons. J. Comp. Neurol. 349, 148–164.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F., Zubricki, E. M., Shipley, M. T., Norman, A. B., and Sanberg, P. R. (1991) Female rats are more sensitive to the locomotor alterations following quinolinic acid-induced striatal lesions: effects of striatal transplants. Exp. Neurol. 111, 369–378.

    Article  PubMed  CAS  Google Scholar 

  • Emerich, D. F., Winn, S. R., and Lindner, M. D. (1997b) Continued presence of intrastriatal but not intraventricular polymer-encapsulated PC 12 cells is required for alleviation of behavioral deficits in Parkinsonian rats. Cell Transplant. 5, 589–596.

    Article  Google Scholar 

  • Fahn, S. (1982) Fluctuations of disability in Parkinson’s disease: pathophysiological aspects, in Movement Disorders (Marsden, C. D. and Fahn, S., eds.), Butterworth, London, pp. 123–145.

    Google Scholar 

  • Fischer, W., Wictorin, K., Björklund, A., Williams, L. R., Varon, S., and Gage, F. H. (1987) Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329, 65–67.

    Article  PubMed  CAS  Google Scholar 

  • Freed, W. J., Morihisa, J. M., Spoor, E., Hoffer, B. J., Olson, L., Seiger, A., and Wyatt, R. J. (1981) Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behavior. Nature 292, 351–352.

    Article  PubMed  CAS  Google Scholar 

  • Frim, D. M., Schumacher, J. M., Short, M. P., Breakefield, X. O., and Isacson, O. (1992) Local response to intracerebral grafts of NGF-secreting fibroblasts: induction of a peroxidative enzyme. Soc. Neurosci. Abstr. 18, 1100.

    Google Scholar 

  • Frim, D. M., Simpson, J., Uhler, T. A., Short, M. P., Bossi, S. R., Breakefield, X. O., Isacson, O. (1993a) Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF. J. Neurosci. Res. 35, 452–458.

    Article  PubMed  CAS  Google Scholar 

  • Frim, D. M., Uhler, T. A., Short, M. P., Exedine, Z. D., Klagsbrun, M., Breakefield, X. O., and Isacson, O. (1993b) Effects of biologically delivered NGF, BDNF, and bFGF on striatal excitotoxic lesions. NeuroReport 4, 367–370.

    Article  PubMed  CAS  Google Scholar 

  • Hargraves, R. and Freed, W. J. (1987) Chronic intrastriatal dopamine infusions in rats with unilateral lesions of the substantia nigra. Life Sci. 40, 959–966.

    Article  PubMed  CAS  Google Scholar 

  • Hefti, F. (1986) Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J. Neurosci. 6, 2155–2162.

    PubMed  CAS  Google Scholar 

  • Hefti, F., Hartikka, J., Salviaterra, P., Weiner, W. J., and Mash, D. C. (1986) Localization of nerve growth factor receptors on cholinergic neurons of the human basal forebrain. Neurosci. Lett. 69, 275–281.

    Article  Google Scholar 

  • Kawaja, M. D., Rosenberg, M. B., Yoshida, K., and Gage, F. H. (1992) Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regeneration of their axons in adult rats. J. Neurosci. 12, 2849–2864.

    PubMed  CAS  Google Scholar 

  • Koh, S., Oyler, G. A., and Higgins, G. A. (1989) Localization of nerve growth factor receptor messenger RNA and protein in the adult rat brain. Exp. Neurol. 106, 209–221.

    Article  PubMed  CAS  Google Scholar 

  • Koliatsos, V. E., Applegate, M. D., Knusel, B., Junard, E. O., Burton, L. E., Mobley, W. C., Hefti, F., and Price, D. L. (1991a) Recombinant human nerve growth factor prevents retrograde degeneration of axotomized basal forebrain cholinergic neu-rons in the rat. Exp. Neurol. 112, 161–173.

    Article  PubMed  CAS  Google Scholar 

  • Koliatsos, V. E., Clatterbuck, R. E., Nauta, H. J. W., Knusel, B., Burton, L. E., Hefti, F., Mobley, W. C, and Price, D. L. (1991b) Human nerve growth factor prevents degeneration of basal forebrain cholinergic neurons in primates. Ann. Neurol. 30, 831–840.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Bartus, R. T., Bothwell, M., Schatteman, G., and Gash, D. M. (1988) Nerve growth factor receptor immunoreactivity in the nonhuman primate (Cebus apella): distribution, morphology, and colocalization with cholinergic enzymes. J. Comp. Neurol. 277, 465–486.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Chen, E.-Y., Chu, Y.-P., McDermott, P., Baetge, E. E., and Emerich, D. F. (1997) Intrastriatal but not intraventricular grafts of encapsulated CNTF-producing cells protects against striatal degeneration in a nonhuman primate model of Huntington’s disease. Soc. Neurosci. Abstr, 27, 85.

    Google Scholar 

  • Kordower, J. H., Gash, D. M., Bothwell, M., Hersh, L., and Mufson, E. J. (1989) Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer’s patients. Neurobiol. Aging 10, 287–294.

    Article  Google Scholar 

  • Kordower, J. H., Liu, Y.-T., Winn, S. R., and Emerich, D. F. (1995) Encapsulated PC12 cell transplants into hemiparkinsonian monkeys: a behavioral, neuroanatomical and neurochemical analysis. Cell Transplant. 4, 155–171.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Winn, S. R., Liu, Y.-T., Mufson, E. J., Sladek, J. R., Jr., Baetge, E. E., Hammang, J. P., and Emerich, D. F. (1994) Aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. Proc. Natl. Acad. Sci. USA 91, 10,898–10,902.

    Article  PubMed  CAS  Google Scholar 

  • Korsching, S., Auberger, G., Heuman, R., Scott, J., and Thoenen, H. (1985) Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J. 4, 1389–1393.

    PubMed  CAS  Google Scholar 

  • Lacy, P. E., Hegre, O. H., Gerasimidi-Vazeou, A., Gentile, F. T., and Dionne, K. E. (1991) Maintenance of normoglycemia in diabetic mice by subcutaneous xenografts of encapsulated islets. Science 254, 1782–1784.

    Article  PubMed  CAS  Google Scholar 

  • Langer, R. and Vacanti, J. P. (1993) Tissue engineering. Science 260, 920–925.

    Article  PubMed  CAS  Google Scholar 

  • Lim, F. and Sun, A. M. (1980) Microencapsulated islets as bioartificial endocrine pancreas. Science 210, 908–910.

    Article  PubMed  CAS  Google Scholar 

  • Lindner, M. D. and Emerich, D. F. (1998) Therapeutic potential of a polymer-encapsulated L-DOPA and dopamine-producing cell line in rodent and primate models of Parkinson’s disease. Cell Transplant. 7, 165–174.

    Article  PubMed  CAS  Google Scholar 

  • Lindner, M. D., Kearns, C. E., Winn, S. R., Frydel, B. R., and Emerich, D. F. (1996a) Effects of intraventricular encapsulated hNGF-secreting fibroblasts in aged rats. Cell Transplant. 5, 205–223.

    Article  PubMed  CAS  Google Scholar 

  • Lindner, M. D., Plone, M. A., Francis, J. M., and Emerich, D. F. (1996b) Validation of a rodent model of Parkinson’s disease: evidence of a therapeutic window for oral Sinemet. Brain Res. Bull. 39, 367–372.

    Article  PubMed  CAS  Google Scholar 

  • Lindner, M. D., Plone, M. A., Mullins, T. D., Winn, S. R., Chandonait, S. E., Stott, J. A., Blaney, T. J., Sherman, S. S., and Emerich, D. F. (1997) Somatic delivery of catecholamines in the striatum attenuate parkinsonian symptoms and widen the therapeutic window or oral Sinemet in rats. Exp. Neurol. 145, 130–140.

    Article  PubMed  CAS  Google Scholar 

  • Lysaght, M. J. and Baurmeister, U. (1993) Dialysis, in Kirk-Othmer Encyclopaedia of Chemical Technology 4th ed., Wiley, New York, pp. 59–74.

    Google Scholar 

  • Martinson, L., Pauley, R., Boggs, D., Brauker, J. H., Sternberg, S. M., and Johnson, R. C. (1993) Protection of xenografts with immunoisolation membranes. Cell Transplant. 3, 249–256.

    Google Scholar 

  • Massia, S. P. and Hubbell, J. A. (1990) Covalent surface immobilization of Arg-Gly-Asp-and Tyr-Ile-Gly-Ser-Arg-containing peptides to obtain well-defined cell-adhesive substrates. Anal. Biochem. 187, 292–299.

    Article  PubMed  CAS  Google Scholar 

  • Montero, C. N. and Hefti, F. (1988) Rescue of lesioned septal cholinergic neurons by nerve growth factor: specificity and requirement for chronic treatment. J. Neurosci. 8, 2986–2999.

    PubMed  CAS  Google Scholar 

  • Mooney, D. J., Hansen, L., Vacanti, J. P., Langer, R., Farmer, S., and Ingber, D. (1992) Switching from differentiation to growth in hepatocytes—control by extracellularmatrix. J. CellPhysiol. 151, 497–505.

    CAS  Google Scholar 

  • Mufson, E. J., Bothwell, M., Hersh, L. B., and Kordower, J. H. (1989) Nerve growth factor receptor immunoreactive profiles in the normal aged human basal forebrain: colocalization with cholinergic neurons. J. Comp. Neurol. 285, 196–217.

    Article  PubMed  CAS  Google Scholar 

  • Olson, L., Nordberg, A., von Hoist, H., Backman, L., Ebendal, T., Alafuzoff, I., Amberla, K., Hartvig, P., Herlitz, A., Lilja, A., Lundqvist, H., Langstrom, B., Meyerson, B., Persson, A., Vlitanen, M., Winblad, B., and Seiger, A. (1992) Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report). J. Neuronal Transm. 4, 479–495.

    Google Scholar 

  • Perlow, M. J., Freed, W. J., Seiger, A., Olson, L., and Wyatt, R. J. (1979) Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science 204, 643–647.

    Article  PubMed  CAS  Google Scholar 

  • Rotem, A., Toner, M., Tompkins, R. G., and Yarmush, M. L. (1992) Oxygen-uptake rates in cultured hepatocytes. Biotechnol. Bioeng. 40, 1286–1291.

    Article  PubMed  CAS  Google Scholar 

  • Sagen, J., Wang, H., Tresco, P. A., and Aebischer, P. (1993) Transplants of immunologically isolate xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances. J. Neurosci. 13, 2415–2423.

    PubMed  CAS  Google Scholar 

  • Sagot, Y., Tan, S. A., Baetge, E. E., Schmalbruch, H., Kato, A. C., and Aebischer, P. (1995) Polymer encapsulated cell lines genetically engineered to release ciliary neurotrophic factor can slow down progressive motor neuronopathy in the mouse. Eur. J. Neurosci. 7, 1313–1320.

    Article  PubMed  CAS  Google Scholar 

  • Sanberg, P. R., Calderon, S. F., Garver, D. L., and Norman, A. B. (1987) Brain tissue transplants in an animal model of Huntington’s disease. Psychopharmacol. Bull. 23, 476–482.

    Google Scholar 

  • Sanberg, P. R., Calderon, S. F., Giordano, M, Tew, J. M., and Norman, A. B. (1989) Quinolinic acid model of Huntington’s disease: locomotor abnormalities. Exp. Neurol. 105, 45–53.

    Article  PubMed  CAS  Google Scholar 

  • Sanberg, P. R., Henault, M. A., and Deckel, A. W. (1986) Locomotor hyperactivity: effects of multiple striatal transplants in an animal model of Huntington’s disease. Pharmacol. Biochem. Behav. 25, 297–300.

    Article  PubMed  CAS  Google Scholar 

  • Schumacher, J. M., Short, M. P., Hyman, B. T., Breakefield, X. O., and Isacson, O. (1991) Intracerebral implantation of nerve growth factor-producing fibroblasts protects striatum against neurotoxic levels of excitatory amino acids. Neuroscience 45, 561–570.

    Article  PubMed  CAS  Google Scholar 

  • Schwab, M. E., Otten, U., Agid, Y., and Thoenen, H. (1979) Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra. Brain Res. 168, 473–483.

    Article  PubMed  CAS  Google Scholar 

  • Segal, M., Greenberger, V., and Pearl, E. (1989) Septal transplants ameliorate spatial deficits and restore cholinergic function in rats with a damaged septohippocampal connection. Brain Res. 500, 139–148.

    Article  PubMed  CAS  Google Scholar 

  • Seiler, M. and Schwab, M. E. (1984) Specific retrograde transport of nerve growth factor (NGF) from cortex to nucleus basalis in the rat. Brain Res. 300, 33–39.

    Article  PubMed  CAS  Google Scholar 

  • Sheldon, D. L. and Reichardt, L. F. (1986) Studies on the expression of beta NGF gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several neuronal populations. Proc. Natl. Acad. Sci. USA 83, 2714–2718.

    Article  Google Scholar 

  • Steininger, T. L., Wainer, B. H., Klein, H., Barbacid, M., and Palfrey, H. C. (1993) High affinity nerve growth factor receptor (trk) immunoreactivity is localized in cholinergic neurons of the basal forebrain and striatum in the adult rat. Brain Res. 612, 330–335.

    Article  PubMed  CAS  Google Scholar 

  • Strathmann, H. (1985) Production of microporous media by phase inversion processes, in Material Science of Synthetic Membranes (Lloyd, D. R., ed.), American Chemical Society, Washington DC, pp. 165–196.

    Chapter  Google Scholar 

  • Subramanian, T., Emerich, D. F., Bakay, R. A. E., Hoffman, J. M., Goodman, M. M., Shoup, T. M., Miller, G. W., Levey, A. I., Hubert, G. W., Batchelor, S., Winn, S. R., Saydoff, J. A., and Watts, R. L. (1997) Polymer-encapsulated PC12 cells demonstrate high affinity uptake of dopamine in vitro and 18F-dopa uptake and metabolism after intracerebral implantation in nonhuman primates. Cell Transplant. 6, 469–477.

    Article  PubMed  CAS  Google Scholar 

  • Tresco, P. A., Winn, S. R., Jaeger, C. B., Greene, L. A., and Aebischer, P. (1992) Poly-merencapsulated PC12 cells: Longterm survival and associated reduction in lesioned-induced rotational behavior. Cell Transplant. 1, 255–264.

    PubMed  CAS  Google Scholar 

  • Tuszynski, M. H., U, H. S., Amaral, D. G., and Gage, F. H. (1990) Nerve growth factor infusion in the primate brain reduces lesion-induced cholinergic neuronal degeneration. J. Neurosci. 10, 3604–3614.

    PubMed  CAS  Google Scholar 

  • Tuszynski, M. H., U, H. S., Yoshida K., and Gage, F. H. (1991) Recombinant human nerve factor infusions prevent cholinergic neuronal degeneration in the adult primate brain. Ann. Neurol. 30, 625–636.

    Article  PubMed  CAS  Google Scholar 

  • Vahlsing, H. L., Varon, S., Hagg, T., Fass-Holmes, B., Dekker, A., Mamley, M., and Manthorpe, M. (1989) Improved device for continuous intraventricular infusions prevents the introduction of pump-derived toxins and increases the effectiveness of NGF treatments. Exp. Neurol. 105, 233–243.

    Article  PubMed  CAS  Google Scholar 

  • Wang, N., Butler, J. P., and Ingber, D. E. (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127.

    Article  PubMed  CAS  Google Scholar 

  • Winn, S. R., Aebischer, P., and Galletti, P. M. (1989) Brain tissue reaction to perm-selective polymer capsules. J. Biomed. Mater. Res. 23, 31–44.

    Article  PubMed  CAS  Google Scholar 

  • Winn, S. R., Hammang, J. P., Emerich, D. F., Lee, A., Palmiter, R. D., and Baetge E. E. (1994) Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons. Proc. Natl. Acad. Sci. USA 91, 2324–2328.

    Article  PubMed  CAS  Google Scholar 

  • Winn, S. R., Lindner, M. D., Haggett, G., Francis, J. M., and Emerich, D. F. (1996) Polymer-encapsulated genetically-modified cells continue to secrete human nerve growth factor for over one year in rat ventricles: behavioral and anatomical consequences. Exp. Neurol. 140, 126–138.

    Article  PubMed  CAS  Google Scholar 

  • Winn, S. R., Zielinski, B., Tresco, P. A., Signore, A. P., Jaeger, C. B., Greene, L. A., and Aebischer, P. (1991) Behavioral recovery following intrastriatal implantation of microencapsulated PC12 cells. Exp. Neurol. 113, 322–329.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Alkermes Inc., Cambridge, MA

    Dwaine F. Emerich

  2. Department of Plastic and Reconstructive Surgery, Oregon Health Sciences University, Portland, OR

    Shelley R. Winn

Authors
  1. Dwaine F. Emerich
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  2. Shelley R. Winn
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Editor information

Editors and Affiliations

  1. University of Cambridge, Cambridge, UK

    Stephen B. Dunnett

  2. Cardiff University, Cardiff, Wales, UK

    Stephen B. Dunnett

  3. University of Saskatchewan, Saskatoon, Canada

    Alan A. Boulton

  4. University of Alberta, Edmonton, Canada

    Glen B. Baker

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© 2000 Humana Press Inc., Totowa, NJ

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Emerich, D.F., Winn, S.R. (2000). Application of Polymer-Encapsulated Cell Therapy for CNS Diseases. In: Dunnett, S.B., Boulton, A.A., Baker, G.B. (eds) Neural Transplantation Methods. Neuromethods, vol 36. Humana Press. https://doi.org/10.1007/978-1-59259-690-4_13

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  • DOI: https://doi.org/10.1007/978-1-59259-690-4_13

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-793-9

  • Online ISBN: 978-1-59259-690-4

  • eBook Packages: Springer Protocols

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