Abstract
For many years, it was recognized that brain and spinal cord tissues could not be regenerated once they were damaged. Recently, this concept has been challenged and many basic and clinical studies regarding neural regeneration and transplantation have been reported. In this review, we will summarize the clinical studies using cell transplantation for the treatment of Parkinson’s disease and cerebral ischemia. Then, we will report the recent advancement of basic studies using cell lines and neural stem cells as donor tissue. Cell line grafting can be done by encapsulating desired cell line in semipermeable polymer hollow fibers, and neurotransmitter and neurotrophic factors can be delivered into the brain. Neural stem cells, especially those of adult origin, have the advantage that autologous cell transplantation can be done. The biological features of various types of stem cells have been widely investigated and will be applied to the treatment of neurological disorders through cell transplantation.
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References
Backlund EO, Granberg PO, Hamberger B, Knutsson E, Martensson A, Sedvall G. Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J Neurosurg 1985;62:169–173
Lindvall O, Rehncrona S, Gustavii B, Brundin P, Astedt B, Widner H. Fetal dopamine-rich mesencephalic grafts in Parkinson’s disease. Lancet 1988;2:1483–1484
Itakura T, Komai N, Ryujin Y, Ooiwa Y, Nakai M, Yasui M. Autologous transplantation of the cervical sympathetic ganglion into the parkinsonian brain. Neurosurgery 1994;35:155–157
Date I, Imaoka T, Miyoshi Y, Ono T, Asari S, Ohmoto T. 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. J Neurosurg 1996;84: 685–689
Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J. Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000;55:565–569
Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001;344:710–719
Arjona V, Minguez-Castellanos A, Montoro RJ, Ortega A, Escamilla F, Toledo-Aral JJ. Autotransplantation of human carotid body cell aggregates for treatment of Parkinson’s disease. Neurosurgery 2003;53:321–330
Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 2003;54:403–414
Gill SS, Patel NK, Hotton GR, O’sullivan K, McCarter R, Bunnage M. Direct infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003;9:589–595
Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 2005;102: 216–222
Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005;57: 874–882
Kondziolka D, Steinberg GK, Wechsler L, Meltzer CC, Elder E, Gebel J, Decesare S, Jovin T, Zafonte R, Lebowitz J, Flickinger JC, Tong D, Marks MP, Jamieson C, Luu D, Bell-Stephens T, Teraoka J. Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 2005;103: 38–45
Stover NP, Bakay RA, Subramanian T, Raiser CD, Cornfeldt ML, Schweikert AW, Allen RC, Watts RL. Intrastriatal implantation of human retinal pigment epithelial cells attached to microcarriers in advanced Parkinson disease. Arch Neurol 2005;62:1833–1837
Mínguez-Castellanos A, Escamilla-Sevilla F, Hotton GR, Toledo-Aral JJ, Ortega-Moreno A, Méndez-Ferrer S, Martín-Linares JM, Katati MJ, Mir P, Villadiego J, Meersmans M, Pérez-García M, Brooks DJ, Arjona V, López-Barneo J. Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study. J Neurol Neurosurg Psychiatry 2007;78:825–831
Slevin JT, Gash DM, Smith CD, Gerhardt GA, Kryscio R, Chebrolu H, Walton A, Wagner R, Young AB. Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal. J Neurosurg 2007;106:614–620
Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ. Safety and tolerability of gene therapy with an adeno-associated virus (AAV)-borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet 2007;369:2097–2105
Aoi M, Date I, Tomita S, Ohmoto T. GDNF induces recovery of the nigrostriatal dopaminergic system in the rat brain following intracerebroventricular or intraparenchymal administration. Acta Neurochir 2000;142:805–810
Yasuhara T, Shingo T, Date I. Glial cell line-derived neurotrophic factor (GDNF) therapy for Parkinson’s disease. Acta Med Okayama 2007;61:51–56
Aebischer P, Schluep M, Deglon N, Joseph JM, Hirt L, Heyd B. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Med 1996;2:696–699
Date I, Shingo T, Yoshida H, Fujiwara K, Kobayashi K, Takeuchi. Grafting of encapsulated dopamine-secreting cells in Parkinson’s disease: long-term primate study. Cell Transplant 2000;9:705–709
Shingo T, Date I, Yoshida H, Ohmoto T. Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNFproducing cells in a rat model of Parkinson’s disease. J Neurosci Res 2002;69:946–954
Kobayashi K, Yasuhara T, Agari T, Muraoka K, Kameda M, Ji Yuan W, Hayase H, Matsui Y, Shingo T, Date I. Control of dopamine- secretion by Tet-Off system in an in vivo model of parkinsonian rat. Brain Res 2006;1102:1–11
Yasuhara T, Shingo T, Kobayashi K, Takeuchi A, Yano A, Muraoka K. Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease. Eur J Neurosci 2004;19:1494–1504
Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992;255:1707–1710
Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Peterson AC, Reynolds BA. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 1996; 16:7599–7609
Palmer TD, Takahashi J, Gage FH. The adult rat hippocampus contains primordial neural stem cells. Mol Cell Neurosci 1997;8: 389–404
Hagell P, Brundin P. Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease. J Neuropathol Exp Neurol 2001;60:741–752
Svendsen CN, Caldwell MA, Shen J, ter Borg MG, Rosser AE, Tyers P, Karmiol S, Dunnett SB. 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
Studer L, Csete M, Lee SH, Kabbani N, Walikonis J, Wold B, McKay R. Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 2000;20:7377–7383
Sanchez-Pernaute R, Studer L, Bankiewicz KS, Major EO, McKay RD. In vitro generation and transplantation of precursor-derived human dopamine neurons. J Neurosci Res 2001;65:284–288
Storch A, Paul G, Csete M, Boehm BO, Carvey PM, Kupsch A, Schwarz J. Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp Neurol 2001;170:317–325
Carvey PM, Ling ZD, Sortwell CE, Pitzer MR, McGuire SO, Storch A, Collier TJ. A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson’s disease. Exp Neurol 2001;171:98–108
Wagner J, Akerud P, Castro DS, Holm PC, Canals JM, Snyder EY, Perlmann T, Arenas E. Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Nat Biotechnol 1999;17:653–659
Kim JY, Koh HC, Lee JY, Chang MY, Kim YC, Chung HY, Son H, Lee YS, Studer L, McKay R, Lee SH. Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression. J Neurochem 2003;85:1443–1454
Studer L, Tabar V, McKay RD. Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat Neurosci 1998;1:290–295
Shingo T, Weiss S. Robust induction of tyrosine hydroxylase in embryonic and adult striatal neural stem cell-derived neurons in defined media and the absence of gene transfer. Soc Neurosci Abstr 2000;26:830
Muraoka K, Shingo T, Yasuhara T, Kameda M, Yuen WJ, Uozumi T, Matsui T, Miyoshi Y, Date I. Comparison of the therapeutic potential of adult and embryonic neural precursor cells in a rat model of Parkinson disease. J Neurosurg 2008;108:149–159
Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 2004;113:1701–1710
Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T, Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 2005;115:102–109
Yasuhara T, Matsukawa N, Hara K, Yu G, Xu L, Maki M, Kim SU, Borlongan CV. Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson’s disease. J Neurosci 2006;26:12497–12511
Yano A, Shingo T, Takeuchi A, Yasuhara T, Kobayashi K, Takahashi K, Date I. Encapsulated vascular endothelial growth factor-secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia. J Neurosurg 2005;103:104–114
Muraoka K, Shingo T, Yasuhara T, Kameda M, Wenji Y, Hayase H, Date I. The high integration and differentiation potential of autologous neural stem cell transplantation compared with allogeneic transplantation in adult rat hippocampus. Exp Neurol 2006; 199:311–327
Kameda M, Shingo T, Takahashi K, Muraoka K, Kurozumi K, Yasuhara T, Maruo T, Tsuboi T, Uozumi T, Matsui T, Miyoshi Y, Hamada H, Date I. Adult neural stem and progenitor cells modified to secrete GDNF can protect, migrate and integrate after intracerebral transplantation in rats with transient forebrain ischemia. Eur J Neurosci 2007;26:1462–1478
Date I, Shingo T, Yasuhara T, Takahashi K, Muraoka K. Neuroprotection and repair by using adult-derived neural stem cell grafting for neurological disorders. In: Kanno T, Kato Y (eds) Minimally invasive neurosurgery and multidisciplinary neurotraumatology. Tokyo: Springer-Verlag, 2006;131-137
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This article is modified from “Neural regeneration: treatment of Parkinson’s disease and cerebral ischemia,” by the same authors, in Jinkozoki 2007;36:130–133
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Date, I., Yasuhara, T. Neurological disorders and neural regeneration, with special reference to Parkinson’s disease and cerebral ischemia. J Artif Organs 12, 11–16 (2009). https://doi.org/10.1007/s10047-008-0441-4
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DOI: https://doi.org/10.1007/s10047-008-0441-4