Abstract
1. Accumulating evidence indicates that damaged brain functions can be ameliorated in a variety of animal models by the grafting of fetal neuronal cell or tissue into damaged brain. Clinical trials are under way to determine whether human fetal mesencephalic tissue can ameliorate motor functions in patients with Parkinson's disease.
2. Autopsy findings of parkinsonian patient implanted with human fetal mesencephalic tissue clearly revealed that the fetal neuronal graft can survive for an extended period of time in the human brain and densely reinnervate the surrounding host striatal tissue.
3. It is, however, still important to obtain more practical, effective, and ethically justifiable donor material for the future clinical application of the procedures. Desirable properties for the donor cells include long-term survival in the brain, neuronal cell type for the reconstruction of damaged neural circuits, and susceptibility to genetic manipulation for the practical use.
4. With the development of molecular biology techniques, genetic modification and transplantation of the donor neuronal cells might be a feasible way to cure many kinds of central nervous system diseases toward a “graft-gene therapy.”
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REFERENCES
Apuzzo, M. L. J., Neal, J. H., Waters, C. H., Appley, A. J., Boyd, S. D., Couldwell, W. T., Wheelock, V. H., and Weiner, L. P. (1990). Utilization of unilateral and bilateral rationale, techniques, and observations. Neurosurgery 26:746–757.
Björklund, A. (1991). Neural transplantation—An experimental tool with clinical possibilities. TINS 14:319–322.
Buse, E., and Krisch, B. (1987). The mouse neural plate as starting material for studying neuronal differentiation in vitro. Anat. Embryol. 175:331–340.
Chan, W. Y., and Tam, P. P. L. (1986). The histogenetic potential of neural plate cells of early-somite-stage mouse embryos. J. Embryol. Exp. Morphol. 96:183–193.
Ernfors, P., Ebendal, T., Olson, L., Mouton, P., Strömberg, I., and Persson, H. (1989). A cell line producing recombinant nerve growth factor evokes growth responses in intrinsic and grafted central cholinergic neurons. Proc. Natl. Acad. Sci. USA 86:4756–4760.
Fisher, L. J., Jinnah, H. A., Kale, L. C., Higgins, G. A., and Gage, F. H. (1991). Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa. Neuron 6:371–380.
Frim, D. M., Wüllner, U., Beal, M. F., and Isacson, O. (1994). Implanted NGF-producing fibroblasts induce catalase and modify ATP levels but do not affect glutamate receptor binding or NMDA receptor expression in the rat striatum. Exp. Neurol. 128:172–180.
Geller, A. I., and Breakefield, X. O. (1988). A defective HSV-1 vector expresses Escherichia coli β-galactosidase in cultured peripheral neurons. Science 241:1667–1669.
Goetz, C. G., Olanow, C. W., Koller, W. C., Penn, R. D., Cahill, D., Morantz, R., Stebbins, G., Tanner, C. M., Klawans, H. L., Shannon, K. M., Comella, C. L., Witt, T., Cox, C., Waxman, M., and Gauger, L. (1989). Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease. N. Engl. J. Med. 320:337–341.
Gossler, A., Joyner, A. L., Rossant, J., and Skarnes, W. C. (1989). Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes. Science 244:463–465.
Horellou, P., Brundin, P., Kalén, P., Mallet, J., and Björklund, A. (1990). In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated rat striatum. Neuron 5:393–402.
Hurtig, H., Joyce, J., Sladek, J. R., Jr., and Trojanowski, J. Q. (1989). Postmortem analysis of adrenal-medulla-to-daudate autograft in a patient with Parkinson's disease. Ann. Neurol. 25:607–614.
James, A. (1993). Transplants with transgenic pig organ? Lancet 342:45.
Jankovic, J., Grossman, R., Goodman, C., Pirozzolo, F., Schneider, L., Zhu, Z., Scardino, P., Garber, A. J., Jhingran, S. G., and Martin, S. (1989). Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson's disease. Neurology 39:1227–1234.
Jiao, S., Gurevich, V., and Wolff, J. A. (1993). Long-term correction of rat model of Parkinson's disease by gene therapy. Nature 362:450–453.
Jirikowski, G. F., Paolo, Sanna, P., Maciejewski-Lenoir, D., and Bloom, F. E. (1992). Reversal of diabetes insipidus in Brattleboro rats: intrahypothalamic injection of vasopressin mRNA. Science 255:996–998.
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.
Kordower, J. H., Freeman, T. B., Snow, B. J., Vingerhoets, F. J. G., Mufson, E. J., Sanberg, P. R., Hauser, R. A., Smith, D. A., Nauert, G. M., Oerl, D. P., and Olanow C. W. (1995). Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease. N. Engl. J. Med. 332:1118–1124.
Lindvall, O. (1991). Prospects of transplantation in human neurodegenerative diseases. TINS 14:376–384.
Lindvall, O., Brundin, P., Widner, H., Rehncrona, S., Gustavii, B., Frackowiak, R., Leenders, K. L., Sawle, G., Rothwell, J. C., Marsden, C. D., and Björklund, A. (1990). Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science 247:574–577.
Peterson, D. I., Price, M. L., and Small, C. S. (1989). Autopsy findings in a patient who had an adrenal-to-brain transplant for Parkinson's disease. Neurology 39:235–238.
Rosenberg, M. B., Friedmann, T., Robertson, R. C., Tuszynski, M., Wolff, J. A., Breakefield, X. O., and Gage, F. H. (1988). Grafting genetically modified cells to the damaged brain: Restorative effects of NGF expression. Science 242:1575–1578.
Skarnes, W. C., Auerbach, B.A., and Joyner A. L. (1992). A gene trap approach in mouse embryonic stem cells: The lacZ reporter is activated by splicing, reflects endogenous gene expression, and is mutagenic in mice. Genes Dev. 6:903–918.
Sotelo, C., and Alvarado-Mallart, R. M. (1991). The reconstruction of cerebellar circuits. TINS 14:350–355.
Uchida, K., Takamatsu, K., Kaneda, N., Toya, S., Tsukada, Y., Kurosawa, Y., Fujita, K., Nagatsu, T., and Kohsaka, S. (1989). Synthesis of L-3,4-dihydroxyphenylalanine by tyrosine hydroxylase cDNA-transfected C6 cells: application for intracerebral grafting. J. Neurochem. 53:728–732.
Uchida, K., Tsuzaki, N., Nagatsu, T., and Kohsaka, S. (1992). Tetrahydrobiopterin-dependent functional recovery in 6-hydroxydopamine-treated rats by intracerebral grafting of fibroblasts transfected with tyrosine hydroxylase cDNA. Dev. Neurosci. 14:173–180.
Uchida, K., Kawaja, M. D., Toya, S., and Roach, A. H. (1995). Transgenic neural plate contributes neuronal cells that survive greater than one year when transplanted into the adult mouse central nervous system. Exp. Neurol. 132:194–208.
Whittemore, S. R., Holets, V. R., Keane, R. W., Levy, D. J., and McKay, R. D. G. (1991). Transplantation of a temperature-sensitive, nerve growth factor-secreting, neuroblastoma cell line into adult rats with fimbria-fornix lesions rescues cholinergic septal neurons. J. Neurosci. Res. 28:156–170.
Wolff, J. A., Fisher, L. J., Xu, L., Jinnah, H. A., Langlais, P. J., Iuvone, P. M., O'Malley, K. L., Rosenberg, M. B., Shimohama, S., Friedmann, T., and Gage, F. H. (1989). Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease. Proc. Natl. Acad. Sci. USA 86:9011–9014.
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Uchida, K., Roach, A.H., Kawaja, M.D. et al. Successful Survival of Grafted Transgenic Neural Plate Cells in Adult Central Nervous System Environment. Cell Mol Neurobiol 19, 79–86 (1999). https://doi.org/10.1023/A:1006916624755
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DOI: https://doi.org/10.1023/A:1006916624755