Chondroitin sulfate, a major niche substance of neural stem cells, and cell transplantation therapy of neurodegeneration combined with niche modification

Current Stem Cell Research and Therapy

Volumn 4, Issue 3, 2009, Pages 200-209

  Sato, Yoshiaki ^a,b   Oohira, Atsuhiko ^c  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c AICHI MEDICAL UNIVERSITY   (Japan)

Author keywords

Chondroitin sulfate; Extracellular matrix; Neurodegenerative diseases; Niche; Proteoglycan; Stem cells; Transplantation

Indexed keywords

CHONDROITIN SULFATE;

CELL PROLIFERATION; CELL REGENERATION; CELL TYPE; CENTRAL NERVOUS SYSTEM; EXTRACELLULAR MATRIX; HUMAN; HYPOXIA; ISCHEMIA; NERVE CELL DIFFERENTIATION; NERVE CELL NETWORK; NERVE DEGENERATION; NEURAL STEM CELL; NEUROLOGIC DISEASE; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SPINE INJURY; STEM CELL TRANSPLANTATION; TISSUE INJURY;

EID: 74849120819     PISSN: 1574888X     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488809789057419     Document Type: Review

References (115)

1. Oohira A, Matsui F, Matsuda M, Shoji R. Developmental change in the glycosaminoglycan composition of the rat brain. J Neurochem 1986; 47: 588-93.
2. Bandtlow CE, Zimmermann DR. Proteoglycans in the developing brain: new conceptual insights for old proteins. Physiol Rev 2000; 80: 1267-90.
3. Oohira A. Multiple species and functions of proteoglycans in the central nervous system. In: Kamerling H Ed. Comprehensive Glycoscience: From Chemistry to Systems Biology. Cell Glycobiology and Development Oxford Elsevier Ltd 2007; Vol. 4: pp. 297-322.
4. Whitelock JM, Iozzo RV. Heparan sulfate: a complex polymer charged with biological activity. Chem Rev 2005; 105: 2745-64.
5. Brickman YG, Ford MD, Gallagher JT, Nurcombe V, Bartlett PF, Turnbull JE. Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development. J Biol Chem 1998; 273: 4350-9.
6. Iseki K, Hagino S, Mori T, et al. Increased syndecan expression by pleiotrophin and FGF receptor-expressing astrocytes in injured brain tissue. Glia 2002; 39: 1-9.
7. Muramatsu T. Roles of Proteoglycans in Reception of the Midkine Signal. Trends Glycosci Glycotechnol 2001; 13: 563-72.
8. Raulo E, Chernousov MA, Carey DJ, Nolo R, Rauvala H. Isolation of a neuronal cell surface receptor of heparin binding growthassociated molecule (HB-GAM). Identification as N-syndecan (syndecan-3). J Biol Chem 1994; 269: 12999-3004.
9. Yamaguchi Y. Heparan sulfate proteoglycans in the nervous system: their diverse roles in neurogenesis, axon guidance, and synaptogenesis. Semin Cell Dev Biol 2001; 12: 99-106.
10. Kabos P, Matundan H, Zandian M, et al. Neural precursors express multiple chondroitin sulfate proteoglycans, including the lectican family. Biochem Biophys Res Commun 2004; 318: 955-63.
11. Ida M, Shuo T, Hirano K, et al. Identification and functions of chondroitin sulfate in the milieu of neural stem cells. J Biol Chem 2006; 281: 5982-91.
12. Sirko S, von Holst A, Wizenmann A, Gotz M, Faissner A. Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 2007; 134: 2727-38.
13. Akita K, von Holst A, Furukawa Y, Mikami T, Sugahara K, Faissner A. Expression of multiple chondroitin/dermatan sulfotransferases in the neurogenic regions of the embryonic and adult central nervous system implies that complex chondroitin sulfates have a role in neural stem cell maintenance. Stem Cells 2008; 26: 798-809.
14. Lamari FN, Karamanos NK. Structure of chondroitin sulfate. Adv Pharmacol 2006; 53: 33-48.
15. Nandini CD, Sugahara K. Role of the sulfation pattern of chondroitin sulfate in its biological activities and in the binding of growth factors. Adv Pharmacol 2006; 53: 253-79.
16. von Holst A, Sirko S, Faissner A. The unique 473HD-Chondroitinsulfate epitope is expressed by radial glia and involved in neural precursor cell proliferation. J Neurosci 2006; 26: 4082-94.
17. Purushothaman A, Fukuda J, Mizumoto S, et al. Functions of chondroitin sulfate/dermatan sulfate chains in brain development. Critical roles of E and iE disaccharide units recognized by a single chain antibody GD3G7. J Biol Chem 2007; 282: 19442-52.
18. Nadanaka S, Clement A, Masayama K, Faissner A, Sugahara K. Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity. J Biol Chem 1998; 273: 3296-307.
19. Ueoka C, Kaneda N, Okazaki I, Nadanaka S, Muramatsu T, Sugahara K. Neuronal cell adhesion, mediated by the heparinbinding neuroregulatory factor midkine, is specifically inhibited by chondroitin sulfate E. Structural ans functional implications of the over-sulfated chondroitin sulfate. J Biol Chem 2000; 275: 37407-13.
20. Deepa SS, Umehara Y, Higashiyama S, Itoh N, Sugahara K. Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. Implications as a physiological binding partner in the brain and other tissues. J Biol Chem 2002; 277: 43707-16.
21. Clement AM, Sugahara K, Faissner A. Chondroitin sulfate E promotes neurite outgrowth of rat embryonic day 18 hippocampal neurons. Neurosci Lett 1999; 269: 125-8.
22. Gama CI, Tully SE, Sotogaku N, et al. Sulfation patterns of glycosaminoglycans encode molecular recognition and activity. Nat Chem Biol 2006; 2: 467-73.
23. Sotogaku N, Tully SE, Gama CI, et al. Activation of phospholipase C pathways by a synthetic chondroitin sulfate-E tetrasaccharide promotes neurite outgrowth of dopaminergic neurons. J Neurochem 2007; 103: 749-60.
24. Sato Y, Nakanishi K, Tokita Y, et al. A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death. J Neurochem 2008; 104: 1565-76.
25. Akiyama H, Sakai S, Linhardt RJ, Goda Y, Toida T, Maitani T. Chondroitin sulphate structure affects its immunological activities on murine splenocytes sensitized with ovalbumin. Biochem J 2004; 382: 269-78.
26. Ma J, Chen T, Mandelin J, et al. Regulation of macrophage activation. Cell Mol Life Sci 2003; 60: 2334-46.
27. Batchelor PE, Liberatore GT, Wong JY, et al. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 1999; 19: 1708-16.
28. Rolls A, Cahalon L, Bakalash S, Avidan H, Lider O, Schwartz M. A sulfated disaccharide derived from chondroitin sulfate proteoglycan protects against inflammation-associated neurodegeneration. FASEB J 2006; 20: 547-9.
29. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292: 154-6.
30. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 1981; 78: 7634-8.
31. 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: 2344-9.
32. Bain G, Kitchens D, Yao M, Huettner JE, Gottlieb DI. Embryonic stem cells express neuronal properties in vitro. Dev Biol 1995; 168: 342-57.
33. Fraichard A, Chassande O, Bilbaut G, Dehay C, Savatier P, Samarut J. In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J Cell Sci 1995; 108 (Pt 10): 3181-8.
34. Strubing C, Ahnert-Hilger G, Shan J, Wiedenmann B, Hescheler J, Wobus AM. Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mech Dev 1995; 53: 275-87.
35. Okabe S, Forsberg-Nilsson K, Spiro AC, Segal M, McKay RD. Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mech Dev 1996; 59: 89-102.
36. Bithell A, Williams BP. Neural stem cells and cell replacement therapy: making the right cells. Clin Sci (Lond) 2005; 108: 13-22.
37. Johe KK, Hazel TG, Muller T, Dugich-Djordjevic MM, McKay RD. Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev 1996; 10: 3129-40.
38. Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4: 1313-7.
39. Luskin MB. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 1993; 11: 173-89.
40. Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 1999; 2: 260-5.
41. Morshead CM, Reynolds BA, Craig CG, et al. Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 1994; 13: 1071-82.
42. Roy NS, Wang S, Jiang L, et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med 2000; 6: 271-7.
43. Horiguchi S, Takahashi J, Kishi Y, et al. Neural precursor cells derived from human embryonic brain retain regional specificity. J Neurosci Res 2004; 75: 817-24.
44. Nery S, Fishell G, Corbin JG. The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nat Neurosci 2002; 5: 1279-87.
45. Hack MA, Sugimori M, Lundberg C, Nakafuku M, Gotz M. Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6. Mol Cell Neurosci 2004; 25: 664-78.
46. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000; 164: 247-56.
47. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61: 364-70.
48. Sanchez-Ramos JR, Song S, Kamath SG, et al. Expression of neural markers in human umbilical cord blood. Exp Neurol 2001; 171: 109-15.
49. Li Y, Chen J, Wang L, Lu M, Chopp M. Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 2001; 56: 1666-72.
50. Hardy SA, Maltman DJ, Przyborski SA. Mesenchymal stem cells as mediators of neural differentiation. Curr Stem Cell Res Ther 2008; 3: 43-52.
51. Chen J, Sanberg PR, Li Y, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 2001; 32: 2682-8.
52. Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001; 32: 1005-11.
53. Chen X, Li Y, Wang L, et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology 2002; 22: 275-9.
54. Brazelton TR, Rossi FM, Keshet GI, Blau HM. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000; 290: 1775-9.
55. Garbuzova-Davis S, Willing AE, Zigova T, et al. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res 2003; 12: 255-70.
56. Muenzer J, Fisher A. Advances in the treatment of mucopolysaccharidosis type I. N Engl J Med 2004; 350: 1932-4.
57. Willing AE, Lixian J, Milliken M, et al. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res 2003; 73: 296-307.
58. Joannides A, Gaughwin P, Schwiening C, et al. Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cells. Lancet 2004; 364: 172-8.
59. Abuljadayel IS. Induction of stem cell-like plasticity in mononuclear cells derived from unmobilised adult human peripheral blood. Curr Med Res Opin 2003; 19: 355-75.
60. Zhao Y, Glesne D, Huberman E. A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc Natl Acad Sci USA 2003; 100: 2426-31.
61. Mitchell KE, Weiss ML, Mitchell BM, et al. Matrix cells from Wharton's jelly form neurons and glia. Stem Cells 2003; 21: 50-60.
62. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-76.
63. Lindvall O, Bjorklund A. Cell therapy in Parkinson's disease. NeuroRx 2004; 1: 382-93.
64. Dezawa M, Kanno H, Hoshino M, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 2004; 113: 1701-10.
65. Parish CL, Castelo-Branco G, Rawal N, et al. Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice. J Clin Invest 2008; 118: 149-60.
66. Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med 2004; 10(Suppl): S42-50.
67. Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 2002; 110: 429-41.
68. Dunnett SB, Rosser AE. Stem cell transplantation for Huntington's disease. Exp Neurol 2007; 203: 279-92.
69. Dunnett SB, Rosser AE. Cell therapy in Huntington's disease. NeuroRx 2004; 1: 394-405.
70. Bachoud-Levi AC, Remy P, Nguyen JP, et al. Motor and cognitive improvements in patients with Huntington's disease after neural transplantation. Lancet 2000; 356: 1975-9.
71. Nagai M, Re DB, Nagata T, et al. Astrocytes expressing ALSlinked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 2007; 10: 615-22.
72. Cassina P, Peluffo H, Pehar M, et al. Peroxynitrite triggers a phenotypic transformation in spinal cord astrocytes that induces motor neuron apoptosis. J Neurosci Res 2002; 67: 21-9.
73. Clement AM, Nguyen MD, Roberts EA, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 2003; 302: 113-7.
74. Corti S, Locatelli F, Papadimitriou D, et al. Neural stem cells LewisX+ CXCR4+ modify disease progression in an amyotrophic lateral sclerosis model. Brain 2007; 130: 1289-305.
75. Colello RJ, Pott U, Schwab ME. The role of oligodendrocytes and myelin on axon maturation in the developing rat retinofugal pathway. J Neurosci 1994; 14: 2594-605.
76. Sanchez I, Hassinger L, Paskevich PA, Shine HD, Nixon RA. Oligodendroglia regulate the regional expansion of axon caliber and local accumulation of neurofilaments during development independently of myelin formation. J Neurosci 1996; 16: 5095-105.
77. Windrem MS, Nunes MC, Rashbaum WK, et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 2004; 10: 93-7.
78. Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 2005; 49: 385-96.
79. Eftekharpour E, Karimi-Abdolrezaee S, Fehlings MG. Current status of experimental cell replacement approaches to spinal cord injury. Neurosurg Focus 2008; 24: E19.
80. Yasuhara T, Matsukawa N, Yu G, et al. Behavioral and histological characterization of intrahippocampal grafts of human bone marrow-derived multipotent progenitor cells in neonatal rats with hypoxic-ischemic injury. Cell Transplant 2006; 15: 231-8.
81. Ma J, Wang Y, Yang J, et al. Treatment of hypoxic-ischemic encephalopathy in mouse by transplantation of embryonic stem cellderived cells. Neurochem Int 2007; 51: 57-65.
82. Matsui F, Oohira A. Proteoglycans and injury of the central nervous system. Congenit Anom (Kyoto) 2004; 44: 181-8.
83. Rhodes KE, Fawcett JW. Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS? J Anat 2004; 204: 33-48.
84. Crespo D, Asher RA, Lin R, Rhodes KE, Fawcett JW. How does chondroitinase promote functional recovery in the damaged CNS? Exp Neurol 2007; 206: 159-71.
85. Moon LD, Asher RA, Rhodes KE, Fawcett JW. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 2001; 4: 465-6.
86. Bradbury EJ, Moon LD, Popat RJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416: 636-40.
87. Yamaguchi Y, Mann DM, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 1990; 346: 281-4.
88. Santra M, Reed CC, Iozzo RV. Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope. J Biol Chem 2002; 277: 35671-81.
89. Asher RA, Morgenstern DA, Fidler PS, et al. Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. J Neurosci 2000; 20: 2427-38.
90. Davies JE, Tang X, Denning JW, Archibald SJ, Davies SJ. Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci 2004; 19: 1226-42.
91. Sivasankaran R, Pei J, Wang KC, et al. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci 2004; 7: 261-8.
92. Grimpe B, Silver J. A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. J Neurosci 2004; 24: 1393-7.
93. Yick LW, Cheung PT, So KF, Wu W. Axonal regeneration of Clarke's neurons beyond the spinal cord injury scar after treatment with chondroitinase ABC. Exp Neurol 2003; 182: 160-8.
94. Yick LW, So KF, Cheung PT, Wu WT. Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma 2004; 21: 932-43.
95. Caggiano AO, Zimber MP, Ganguly A, Blight AR, Gruskin EA. Chondroitinase ABCI improves locomotion and bladder function following contusion injury of the rat spinal cord. J Neurotrauma 2005; 22: 226-39.
96. Barritt AW, Davies M, Marchand F, et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 2006; 26: 10856-67.
97. Zuo J, Neubauer D, Graham J, Krekoski CA, Ferguson TA, Muir D. Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. Exp Neurol 2002; 176: 221-8.
98. Tropea D, Caleo M, Maffei L. Synergistic effects of brain-derived neurotrophic factor and chondroitinase ABC on retinal fiber sprouting after denervation of the superior colliculus in adult rats. J Neurosci 2003; 23: 7034-44.
99. Pizzorusso T, Medini P, Landi S, Baldini S, Berardi N, Maffei L. Structural and functional recovery from early monocular deprivation in adult rats. Proc Natl Acad Sci USA 2006; 103: 8517-22.
100. Krekoski CA, Neubauer D, Zuo J, Muir D. Axonal regeneration into acellular nerve grafts is enhanced by degradation of chondroitin sulfate proteoglycan. J Neurosci 2001; 21: 6206-13.
101. Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD. Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci 2005; 25: 1169-78.
102. Yang LJ, Lorenzini I, Vajn K, Mountney A, Schramm LP, Schnaar RL. Sialidase enhances spinal axon outgrowth in vivo. Proc Natl Acad Sci USA 2006; 103: 11057-62.
103. Houle JD, Tom VJ, Mayes D, Wagoner G, Phillips N, Silver J. Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord. J Neurosci 2006; 26: 7405-15.
104. Ikegami T, Nakamura M, Yamane J, et al. Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury. Eur J Neurosci 2005; 22: 3036-46.
105. Sato Y, Nakanishi K, Hayakawa M, et al. Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. Reprod Sci 2008; 15: 613-20.
106. Mizuno H, Warita H, Aoki M, Itoyama Y. Accumulation of chondroitin sulfate proteoglycans in the microenvironment of spinal motor neurons in amyotrophic lateral sclerosis transgenic rats. J Neurosci Res 2008; 86: 2512-23.
107. Sobel RA, Ahmed AS. White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. J Neuropathol Exp Neurol 2001; 60: 1198-207.
108. DeWitt DA, Silver J. Regenerative failure: a potential mechanism for neuritic dystrophy in Alzheimer's disease. Exp Neurol 1996; 142: 103-10.
109. Suzuki T, Akimoto M, Imai H, et al. Chondroitinase ABC treatment enhances synaptogenesis between transplant and host neurons in model of retinal degeneration. Cell Transplant 2007; 16: 493-503.
110. Singhal S, Lawrence JM, Bhatia B, et al. Chondroitin sulfate proteoglycans and microglia prevent migration and integration of grafted muller stem cells into degenerating retina. Stem Cells 2008; 26: 1074-82.
111. Knepper PA, Goossens W, Hvizd M, Palmberg PF. Glycosaminoglycans of the human trabecular meshwork in primary open-angle glaucoma. Invest Ophthalmol Vis Sci 1996; 37: 1360-7.
112. Lawrence JM, Singhal S, Bhatia B, et al. MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics. Stem Cells 2007; 25: 2033-43.
113. Llado J, Haenggeli C, Maragakis NJ, Snyder EY, Rothstein JD. Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors. Mol Cell Neurosci 2004; 27: 322-31.
114. Rolls A, Avidan H, Cahalon L, et al. A disaccharide derived from chondroitin sulphate proteoglycan promotes central nervous system repair in rats and mice. Eur J Neurosci 2004; 20: 1973-83.
115. Kinouchi R, Takeda M, Yang L, et al. Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat Neurosci 2003; 6: 863-8.