ID 13515
Sort Key
Title Alternative
Parkinson's disease from a viewpoint of regenerative medicine
FullText URL
Thumnail 116_17.pdf 6.42 MB
It has long been considered that central nervous system would not regenerate after injury, but this concept has recently been changing due to the development of neuroscience research. Cell grafting, gene transfer and neurotrophic factor administration into the brain and spinal cord are the examples of methods to perform protection and repair. These techniques are expected to be applied to certain neurological disorders such as Parkinson's disease, cerebral ischemia and spinal cord injury. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the nigrostriatal system. Fetal neurons, chromaffin cells, cell lines, certain genes, neural stem cells, ES cells and bone marrow cells have been investigated as donor cells and vectors to treat Parkinson's disease. This review will summarize the history of neural transplantation in Parkinson's disease and features and prospects of each donor will be discussed.
Parkinson's disease
neural transplantation
Publication Title
Published Date
Publisher Alternative
Okayama Medical Association
Start Page
End Page
Content Type
Journal Article
Copyright Holders
Copyright© 岡山医学会
File Version
Eprints Journal Name
1) Date I, Ohmoto T: Neural transplantation and trophic factors in Parkinson's disease: special reference tchromaffin cell grafting, NGF support from pretransected peripheral nerve and encapsulated dopamine-secreting cell grafting. Exp Neurol (1996) 137, 333-344.
2) Date I: Parkinson's disease, trophic factors, and adrenal medullary chromaffin cell grafting: basic and clinical studies. Brain Res Bull (1996) 40, 1-19.
3) Lindvall O, Brundin P, Widner H, et al.: Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science (1990) 247, 574-577.
4) Freed CR, Greene PE, Breeze RE, et al.: Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med (2001) 344, 710-719.
5) Olanow CW, Goetz CG, Kordower JH, et al.: A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol (2003) 54, 403-414.
6) Madrazo I, Drucker-Colin R, Diaz V, et al.: Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease. N Engl J Med (1987) 316, 831-834.
7) Date I, Yoshimoto Y, Gohda Y, et al.: Long-term effects of cografts of pretransected peripheral nerve with adrenal medulla in animal models of Parkinson's disease. Neurosurgery (1993) 33, 685-690.
8) Date I, Imaoka T, Miyoshi Y, et al.: Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve: case report. J Neurosurg (1996) 84, 685-689.
9) Arjona V, Minguez-Castellanos A, Montoro RJ, et al.: Autotransplantation of human carotid body cell aggregates for treatment of Parkinson's disease. Neurosurgery (2003) 53, 321-328.
10) Toledo-Aral JJ, Mendez-Ferrer S, Pardal R, et al.: Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats. J Neurosci (2003) 23, 141-148.
11) Lin L-FH, Doherty DH, Lile JD, et al.: GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science (1993) 260, 1130-1132.
12) Aoi M, Date I, Tomita S, et al.: The effect of intrastriatal single injection of GDNF on the nigrostriatal dopaminergic system in hemiparkinsonian rats: behavioral and histological studies using two different dosages. Neurosci Res (2000) 36, 319-325.
13) Gill SS, Patel NK, Hotton GR, et al.: Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nature Med (2003) 9, 589-595.
14) Aoi M, Date I, Tomita S, et al.: GDNF induces recovery of the nigrostriatal dopaminergic system in the rat brain ollowing intracerebroventricular or intraparenchymf al administration. Acta Neurochir (2000) 142, 805-810.
15) Aebischer P, Schluep M, Deglon N, et al.: Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Med (1996) 2, 696-699.
16) Date I, Ohmoto T, Imaoka T, et al.: Cografting with polymer-encapsulated human nerve growth factor-secreting cells and chromaffin cell survival and behavioral recovery in hemiparkinsonian rats. J Neurosurg (1996) 84, 1006-1012.
17) Date I, Shingo T, Ohmoto T, et al.: Long-term enhanced chromaffin cell survival and behavioral recovery in hemiparkinsonian rats with co-grafted polymerencapsulated human NGF-secreting cells. Exp Neurol (1997) 147, 10-17.
18) Emerich DF, Winn SR, Christenson L, et al.: A novel approach to neural transplantation in Parkinson's disease: Use of polymer-encapsulated cell therapy. Neurosci Biobehav Rev (1992) 16, 437-447.
19) Yoshida H, Date I, Shingo T, et al.: Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease: a preclinical primate study. J Neurosurg (2003) 98, 874-881.
20) Date I, Shingo T, Yoshida H, et al.: Grafting of encapsulated dopamine-secreting cells in Parkinson's disease: long-term primate study. Cell Transplantation (2000) 9, 705-709.
21) Subramanian T, Emerich DF, Bakay RA, et al.: Polymerencapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-Dopa uptake and metabolism after intracerebral implantation in nonhuman primates. Cell Transplantation (1997) 6, 469-477.
22) Date I, Shingo T, Yoshida H, et al.: Grafting of encapsulated genetically modified cells secreting GDNF into the striatum of parkinsonian model rats. Cell Transplantation (2001) 10, 397-401.
23) Uchida S, Suzuki Y, Araie M, et al.: Factors secreted by human amniotic epithelial cells promote the survival of rat retinal ganglion cells. Neurosci Lett (2003) 341, 1-4.
24) Svendsen CN, Caldwell MA, Shen J, et al.: Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease. Exp Neurol (1997) 148, 135-146.
25) Shingo T, Weiss S: Robust induction of tyrosine hydroxylase in embryonic and adult striatal neural stem cellderived neurons in defined media and the absence of gene transfer. Soc Neurosci Abstr (2000) 26, 830.
26) Fallon J, Reid S, Kinyamu R, et al.: In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci USA (2000) 97, 14686-14691.
27) Shingo T, Sorokan ST, Shimazaki T, et al.: Erythropoietin regulates the in vitro and in vivo production of neural progenitor by mammalian forebrain neural stem cells. J Neurosci (2001) 21, 9733-9743.
28) Bjorklund LM, Sanchez-Pernaute R, Chung S, et al.: Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA (2002) 99, 2344-2349.
29) Li Y, Chen J, Wang L, et al.: Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of Parkinson's disease. Neurosci Lett (2001) 316, 67-70.
30) Shingo T, Date I, Yoshida H, et al.: Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNF-producing cells in a rat model of Parkinson's disease. J Neurosci Res (2002) 69, 946-954.
31) Imaoka T, Date I, Ohmoto T, et al.: Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex. Hum Gene Ther (1998) 9, 1093-1102.
32) Kawasaki H, Mizuseki K, Nishikawa S, et al.: Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron (2000) 28, 31-40.