Can we teach old dogs new tricks? neuroprotective cell therapy in Alzheimer's and Parkinson's disease

Journal of Alzheimer's Disease

Volumn 37, Issue 2, 2013, Pages 251-272

  Kazmerova, Zuzana ^a   Zilka, Norbert ^a,b   Cente, Martin ^a,b   Neradil, Peter ^a   Zilkova, Monika ^a   Novak, Michal ^a,b  

^a INSTITUTE OF NEUROIMMUNOLOGY   (Slovakia)

^b Axon Neuroscience SE ^*  (Slovakia)

Author keywords

Alzheimer disease; cell replacement therapy; Parkinson disease; regenerative therapy; stem cells

Indexed keywords

ADULT STEM CELL; ALZHEIMER DISEASE; CELL DIFFERENTIATION; CELL THERAPY; CELL TRANSFORMATION; EMBRYONIC STEM CELL; HEMATOPOIETIC STEM CELL; HUMAN; MESENCHYMAL STEM CELL; MULTIPOTENT STEM CELL; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REVIEW; STEM CELL TRANSPLANTATION; UMBILICAL CORD BLOOD;

ALZHEIMER DISEASE; CELL- AND TISSUE-BASED THERAPY; HUMANS; PARKINSON DISEASE; STEM CELLS;

EID: 84883807360     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-130572     Document Type: Review

References (172)

1. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni L, Gannon B, Jones DH, Jennum P, Jordanova A, Jönsson L, Karampampa K, Knapp M,Kobelt G,Kurth T, Lieb R, Linde M, Ljungcrantz C, Maercker A, Melin B, Moscarelli M, Musayev A, Norwood F, Preisig M, Pugliatti M, Rehm J, Salvador-Carulla L, Schlehofer B, Simon R, Steinhausen HC, Stovner LJ, Vallat JM, den Bergh PV, van Os J, Vos P, XuW,Wittchen HU, Jönsson B, Olesen J; CDBE2010Study Group (2011) Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21, 718-779.
2. Olesen J, Gustavsson A, Svensson M,Wittchen HU, Jönsson B, CDBE2010 study group; European Brain Council (2012) The economic cost of brain disorders in Europe. Eur J Neurol 19, 155-262.
3. Rubinsztein DC (2006) The roles of intracellular proteindegradation pathways in neurodegeneration. Nature 443, 780-786.
4. Bredesen DE, Rao RV, Mehlen P (2006) Cell death in the nervous system. Nature 443, 796-802.
5. Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: Origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17, 387- 403.
6. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.
7. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156.
8. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78, 7634-7638.
9. Thomson JA, Marshall VS (1998) Primate embryonic stem cells. Curr Top Dev Biol 38, 133-165.
10. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147.
11. Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2003) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22, 53-54.
12. Baker DE, Harrison NJ, Maltby E, Smith K, Moore HD, Shaw PJ, Heath PR, Holden H, Andrews PW (2007) Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol 25, 207-215.
13. Lefort N, Feyeux M, Bas C, F́eraud O, Bennaceur-Griscelli A, Tachdjian G, Peschanski M, Perrier AL (2008) Human embryonic stem cells reveal recurrent genomic instability at 20q11.21. Nat Biotechnol 26, 1364-1366.
14. Spits C, Mateizel I, Geens M, Mertzanidou A, Staessen C, Vandeskelde Y, Van der Elst J, Liebaers I, Sermon K (2008) Recurrent chromosomal abnormalities in human embryonic stem cells. Nat Biotechnol 26, 1361-1363.
15. Carson CT, Aigner S, Gage FH (2006) Stem cells: The good, bad and barely in control. Nat Med 12, 1237-1238.
16. Robey PG (2000) Stem cells near the century mark. J Clin Invest 105, 1489-1491.
17. Leblond CP (1964) Classification of cell populations on the basis of their proliferative behavior. Natl Cancer Inst Monogr 14, 119-150.
18. TurksenK(2004) Revisiting the bulge. Dev Cell 6, 454-456.
19. Kondo M, Weissman IL, Akashi K (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661-672.
20. Akashi K, Traver D, Miyamoto T, Weissman IL (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193-197.
21. Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D, Arny M, Thomas L, Boyse EA (1989) Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci U S A 86, 3828-3832.
22. Barker JN, Wagner JE (2003) Umbilical cord blood transplantation: Current practice and future innovations. Crit Rev Oncol Hematol 48, 35-43.
23. Baum CM, Weissman IL, Tsukamoto AS, Buckle AM, Peault B (1992) Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci U S A 89, 2804-2808.
24. Patterson JM, Johnson MH, Zimonjic DB, Graubert TA (2000) Characterization of Ly-6M, a novel member of the Ly-6 family of hematopoietic proteins. Blood 95, 3125- 2132.
25. Vodyanik MA, Bork JA, Thomson JA, Slukvin II (2005) Human embryonic stem cell-derived CD34+ cells: Efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood 105, 617-626.
26. Briddell RA, Broudy VC, Bruno E, Brandt JE, Srour EF, Hoffman R (1992) Further phenotypic characterization and isolation of human hematopoietic progenitor cells using a monoclonal antibody to the c-kit receptor. Blood 79, 3159- 3167.
27. Negrin RS, Atkinson K, Leemhuis T, Hanania E, Juttner C, Tierney K, Hu WW, Johnston LJ, Shizurn JA, Stockerl-Goldstein KE, Blume KG, Weissman IL, Bower S, Baynes R, DanseyR, Karanes C, PetersW, Klein J (2000)Transplantation of highly purified CD34+ Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer. Biol Blood Marrow Transplant 6, 262-271.
28. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.
29. Sanchez-Ramos JR (2002) Neural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res 69, 880-893.
30. Herzog EL, Chai L, Krause DS (2003) Plasticity of marrowderived stem cells. Blood 102, 3483-3493.
31. Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1999) Propagation and senescence of human marrow stromal cells in culture: A simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107, 275-281.
32. Oreffo RO, Teti A, Triffitt JT, Francis MJ, Carano A, Zallone AZ (1988) Effect of vitamin A on bone resorption: Evidence for direct stimulation of isolated chicken osteoclasts by retinol and retinoic acid. J Bone Miner Res 3, 203-210.
33. D'Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA (1999) Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 14, 1115-1122.
34. Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1, 92-100.
35. Himes BT, Neuhuber B, Coleman C, Kushner R, Swanger SA, Kopen GC, Wagner J, Shumsky JS, Fischer I (2006) Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord. Neurorehabil Neural Repair 20, 278-296.
36. Zimmet JM, HareJM(2005) Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy. Basic Res Cardiol 100, 471-481.
37. Horwitz EM (2001) Marrow mesenchymal cell transplantation for genetic disorders of bone. Cytotherapy 3, 399-401.
38. Helm GA, Gazit Z (2005) Future uses of mesenchymal stem cells in spine surgery. Neurosurg Focus 19, E13.
39. Mahmood A, Lu D, Wang L, Chopp M (2002) Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. J Neurotrauma 19, 1609-1617.
40. Lee HJ, Lee JK, Lee H, Shin JW, Carter JE, Sakamoto T, Jin HK, Bae JS (2010) The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease. Neurosci Lett 481, 30-35.
41. Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS (2010) Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer's disease mice by modulation of immune responses. Stem Cells 28, 329-343.
42. Abe K (2000) Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury. J Cereb Blood Flow Metab 20, 1393-1408.
43. Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N, Chopp M (2002) Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery. Neurology 59, 514-523.
44. Mahmood A, Lu D, Chopp M (2004) Marrow stromal cell transplantation after traumatic brain injury promotes cellular proliferation within the brain. Neurosurgery 55, 1185-1193.
45. Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG (2006) Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 198, 54-64.
46. Zilka N, Zilkova M, Kazmerova Z, Sarissky M, Cigankova V, Novak M (2011) Mesenchymal stem cells rescue the Alzheimer's disease cell model from cell death induced by misfolded truncated tau. Neuroscience 193, 330-337.
47. Stagg J (2007) Immune regulation by mesenchymal stem cells: Two sides to the coin. Tissue Antigens 69, 1-9.
48. Rasmusson I, Ringden O, Sundberg B, Le Blanc K (2005) Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res 305, 33-41.
49. Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110, 3499-3506.
50. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F, Romagnani P, Maggi E, Romagnani S, Annunziato F (2006) Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24, 386-398.
51. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105, 1815-1822.
52. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31, 890-896.
53. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noel D, Jorgensen C (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102, 3837-3844.
54. Rasmusson I, Ringden O, Sundberg B, Le Blanc K (2003) Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 76, 1208-1213.
55. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Engineering 7, 211-228.
56. Zuk PA, Zhu M, Ashjian P, De UgarteDA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13, 4279-4295.
57. Gimble J, Guilak F (2003) Adipose-derived adult stem cells: Isolation, characterization, and differentiation potential. Cytotherapy 5, 362-369.
58. Safford KM, Hicok KC, Safford SD, Halvorsen YD, WilkisonWO, Gimble JM, Rice HE (2002) Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun 294, 371-379.
59. Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H, Weber RM, Ewerbeck V, Richter W (2003) Cartilage-like gene expression in differentiated human stem cell spheroids: A comparison of bone marrow-derived and adipose tissuederived stromal cells. Arthritis Rheum 48, 418-429.
60. Yoshimura K, Sato K, Aoi N, Kurita M, Inoue K, Suga H, Eto H, Kato H, Hirohi T, Harii K (2008) Cell-assisted lipotransfer for facial lipoatrophy: Efficacy of clinical use of adipose-derived stem cells. Dermatol Surg 34, 1178-1185.
61. Lendeckel S, Jödicke A, Christophis P, Heidinger K, Wolff J, Fraser JK, Hedrick MH, Berthold L, Howaldt HP (2004) Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: Case report. J Craniomaxillofac Surg 32, 370-373.
62. Garcia-Olmo D, Garcia-Arranz M, Herreros D (2008) Expanded adipose-derived stem cells for the treatment of complex perianal fistula including Crohn's disease. Expert Opin Biol Ther 8, 1417-1423.
63. Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, Alfaro M, Rodriguez JP, Harman RJ, Patel AN, Murphy MP, Lee RR, Minev B (2009) Nonexpanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Me 7, 29.
64. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.
65. Stadtfeld M, Hochedlinger K (2010) Induced pluripotency: History, mechanisms, and applications. GenesDev 24, 2239- 2263.
66. Chang MY, Kim D, Kim CH, Kang HC, Yang E, Moon JI, Ko S, Park J, Park KS, Lee KA, Hwang DY, Chung Y, Lanza R, KimKS(2010) Direct reprogramming of rat neural precursor cells and fibroblasts into pluripotent stem cells. PLoS One 5, e9838.
67. Wu Z, Chen J, Ren J, Bao L, Liao J, Cui C, Rao L, Li H, GuY, Dai H, Zhu H, Teng X, Cheng L, Xiao L (2009) Generation of pig induced pluripotent stem cells with a drug-inducible system. J Mol Cell Biol 1, 46-54.
68. Liu H, Zhu F, Yong J, Zhang P, Hou P, Li H, JiangW, Cai J, Liu M, Cui K, Qu X, Xiang T, Lu D, Chi X, Gao G, Ji W, Ding M, Deng H (2008) Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell 3, 587-590.
69. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872.
70. Knoepfler PS (2009) Deconstructing Stem cell tumorigenicity: Aroadmap to safe regenerative medicine. Stem Cells 27, 1050-1056.
71. Pelengaris S, Khan M, Evan G (2002) c-MYC: More than just a matter of life and death. Nat Rev Cancer 2, 764-776.
72. Ponzielli R, Katz S, Barsyte-Lovejoy D, Penn LZ (2005) Cancer therapeutics: Targeting the dark side of Myc. Eur J Cancer 41, 2485-2501.
73. Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322, 945-949.
74. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R,WangW, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766-770.
75. Lin T, Ambasudhan R, Yuan X, LiW, Hilcove S, Abujarour R, Lin X, Hahm HS, Hao E, Hayek A, Ding S (2009) A chemical platform for improved induction of human iPSCs. Nat Methods 6, 805-808.
76. Lakshmipathy U, Davila J, Hart RP (2010) miRNA in pluripotent stem cells. Regen Med 5, 545-555.
77. Mallanna SK, Rizzino A (2010) Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells. Dev Biol 344, 16-25.
78. Redmond DE Jr, Bjugstad KB, Teng YD, Ourednik V, Ourednik J,Wakeman DR, Parsons XH, Gonzalez R, Blanchard BC, Kim SU, Gu Z, Lipton SA, Markakis EA, Roth RH, Elsworth JD, Sladek JR Jr, Sidman RL, Snyder EY (2007) Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Proc Natl Acad Sci U S A 104, 12175-12180.
79. Li LY, Li JT,Wu QY, Li J, Feng ZT, Liu S,Wang TH (2008) Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model of Alzheimer' disease. J Mol Neurosci 34, 157-163.
80. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Müller FJ, Loring JF, Yamasaki TR, Poon WW, Green KN, LaFerlaFM(2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A 106, 13594-13599.
81. Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Bernhard F, Verleysdonk S, Buadze M, Lourhmati A, Klopfer T, Schaumann F, Schmid B, Koehle C, Proksch B,Weissert R, Reichardt HM, van den Brandt J, Buniatian GH, Schwab M, Gleiter CH, Frey Ii WH (2011) Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Res 14, 3-16.
82. Poh KK, Sperry E, Young RG, Freyman T, Barringhaus KG, Thompson CA (2007) Repeated direct endomyocardial transplantation of allogeneic mesenchymal stem cells: Safety of a high dose, "off-the-shelf", cellular cardiomyoplasty strategy. Int J Cardiol 117, 360-364.
83. Lee SR, Lee SH, Moon JY, Park JY, Lee D, Lim SJ, Jeong KH, Park JK, Lee TW, Ihm CG (2010) Repeated administration of bone marrow-derived mesenchymal stem cells improved the protective effects on a remnant kidney model. Ren Fail 32, 840-848.
84. van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ (2010) Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function. J Neurosci 30, 9603- 9611.
85. Berchtold NC, Cotman CW (1998) Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s. Neurobiol Aging 19, 173- 189.
86. Prince MJ, Jackson J (2009) World Alzheimer Report. Alzheimer's Disease International, London.
87. Miniño A, Murphy SL, Xu J, Kochanek K (2011) Deaths: Final Data for 2008. National Vital Statistics Reports. National Center for Health Statistics, Hyattsville, M.D.
88. Alzheimer's, Association (2012) 2012 Alzheimer's disease facts and figures. Alzheimers Dement 8, 131- 168.
89. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83, 4913- 4917.
90. Wischik CM, Novak M, Edwards PC, Klug A, TichelaarW, Crowther RA (1988) Structural characterization of the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A 85, 4884-4888.
91. Wischik CM, Novak M, Thøgersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988) Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A 85, 4506-4510.
92. Novak M, Kabat J, Wischik CM (1993) Molecular characterization of the minimal protease resistant tau unit of the Alzheimer's disease paired helical filament. EMBO J 12, 365-370.
93. Novak M (1994) Truncated tau protein as a new marker for Alzheimer's disease. Acta Virol 38, 173-189.
94. McGeer PL, McGeer EG (1995) The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 21, 195-218.
95. Zilka N, Ferencik M, Hulin I (2006) Neuroinflammation in Alzheimer's disease: Protector or promoter? Bratisl Lek Listy 107, 374-383.
96. ZilkovaM, Koson P, Zilka N (2006) The hunt for dying neurons: Insight into the neuronal loss in Alzheimer's disease. Bratisl Lek Listy 107, 366-373.
97. NikolicWV, Hou H, Town T, Zhu Y, Giunta B, Sanberg CD, Zeng J, Luo D, Ehrhart J, Mori T, Sanberg PR, Tan J (2008) Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular beta-amyloid deposits in Alzheimer mice. Stem Cells Dev 17, 423-439.
98. Kern DS, Maclean KN, Jiang H, Synder EY, Sladek JR, Jr., Bjugstad KB (2011) Neural stem cells reduce hippocampal tau and reelin accumulation in aged Ts65Dn Down syndrome mice. Cell Transplant 20, 371-379.
99. HamptonDW,Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S (2010) Cell-mediated neuroprotection in a mouse model of human tauopathy. J Neurosci 30, 9973- 9983.
100. Lee JH, Chang HS, Kang EH, Chung DJ, Choi CB, Lee JH, Hwang SH, Han H, KimHY(2009) Percutaneous transplantation of human umbilical cord blood-derived multipotent stem cells in a canine model of spinal cord injury. J Neurosurg Spine 11, 749-757.
101. Conner JM, Darracq MA, Roberts J, Tuszynski MH (2001) Non-tropic actions of neurotrophins: Subcortical NGF gene delivery reverses age-related degeneration of primate cortical cholinergic innervation. Proc Natl Acad Sci U S A 98, 1941-1946.
102. Xuan AG, Long DH, Gu HG, Yang DD, Hong LP, Leng SL (2008) BDNF improves the effects of neural stem cells on the rat model of Alzheimer's disease with unilateral lesion of fimbria-fornix. Neurosci Lett 440, 331-335.
103. Xuan AG, Luo M, Ji WD, Long DH (2009) Effects of engrafted neural stem cells in Alzheimer's disease rats. Neurosci Lett 450, 167-171.
104. Desideri G, Cipollone F, Necozione S, Marini C, Lechiara MC, Taglieri G, Zuliani G, Fellin R, Mezzetti A, di Orio F, Ferri C (2008) Enhanced soluble CD40 ligand and Alzheimer's disease: Evidence of a possible pathogenetic role. Neurobiol Aging 29, 348-356.
105. Wang Q, Matsumoto Y, Shindo T, Miyake K, Shindo A, Kawanishi M, Kawai N, Tamiya T, Nagao S (2006) Neural stem cells transplantation in cortex in a mouse model of Alzheimer's disease. J Med Invest 53, 61-69.
106. Moghadam FH, Alaie H, Karbalaie K, Tanhaei S, Nasr Esfahani MH, Baharvand H (2009) Transplantation of primed or unprimed mouse embryonic stem cell-derived neural precursor cells improves cognitive function in Alzheimerian rats. Differentiation 78, 59-68.
107. Chapman RS, Hesketh LJ (2000) Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Disabil Res Rev 6, 84-95.
108. Head E, Lott IT, Patterson D, Doran E, Haier RJ (2007) Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: Targets for nonpharmacological intervention. J Alzheimers Dis 11, 61-76.
109. Lott IT, Head E (2005) Alzheimer disease and Down syndrome: Factors in pathogenesis. Neurobiol Aging 26, 383-389.
110. Li LB, Chang KH,Wang PR, Hirata RK, Papayannopoulou T, RussellDW(2012) Trisomy correction in down syndrome induced pluripotent stem cells. Cell Stem Cell 11, 615-619.
111. Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, Perl DP, Schmeidler J, Kanof P, Davis KL (1995) Neurochemical correlates of dementia severity in Alzheimer's disease: Relative importance of the cholinergic deficits. J Neurochem 64, 749-760.
112. Raivich G, KreutzbergGW(1989) Topography of beta NGF receptor-positive and AChE-reactive neurons in the central nervous system. EXS 57, 50-58.
113. Kaplan DR, Miller FD (2000) Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10, 381-391.
114. Ebendal T, Lönnerberg P, Pei G, Kylberg A, Kullander K, Persson H, Olson L (1994) Engineering cells to secrete growth factors. J Neurol 242, S5-S7.
115. Hefti F (1994) Neurotrophic factor therapy for nervous system degenerative diseases. J Neurobiol 25, 1418-1435.
116. Garcia P, Youssef I, Utvik JK, Florent-B́echard S, Barth́eĺemy V, Malaplate-Armand C, Kriem B, Stenger C, Koziel V, Olivier JL, Escanye MC, Hanse M, Allouche A, Desbène C, Yen FT, Bjerkvig R, Oster T, Niclou SP, Pillot T (2010) Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease. J Neurosci 30, 7516-7527.
117. Bolognin S, Blanchard J, Wang X, Basurto-Islas G, Tung YC, Kohlbrenner E, Grundke-Iqbal I, Iqbal K (2012) An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol 123, 133-151.
118. Blanchard J, Chohan MO, Li B, Liu F, Iqbal K, Grundke-Iqbal I (2010) Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice. J Alzheimers Dis 21, 1185-1195.
119. Blanchard J, Wanka L, Tung YC, Ćardenas-Aguayo Mdel C, LaFerla FM, Iqbal K, Grundke-Iqbal I (2010) Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Aß and tau pathologies in 3xTg-AD mice. Acta Neuropathol 120, 605- 621.
120. Kiyota T, Ingraham KL, Jacobsen MT, Xiong H, Ikezu T (2011) FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders. Proc Natl Acad Sci U S A 108, E1339-E1348.
121. Cardenas-Aguayo Mdel C, Kazim SF, Grundke-Iqbal I, Iqbal K (2013) Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures. PLoS One 8, e53596.
122. Tatebayashi Y, Lee MH, Li L, Iqbal K, Grundke-Iqbal I (2003) The dentate gyrus neurogenesis: A therapeutic target for Alzheimer's disease. Acta Neuropathol 105, 225-232.
123. Chohan MO, Li B, Blanchard J, Tung YC, Heaney AT, Rabe A, Iqbal K, Grundke-Iqbal I (2011) Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiol Aging 32, 1420-1434.
124. Emerich DF, Winn SR, Harper J, Hammang JP, Baetge EE, Kordower JH (1994) Implants of polymer-encapsulated human NGF-secreting cells in the nonhuman primate: Rescue and sprouting of degenerating cholinergic basal forebrain neurons. J Comp Neurol 349, 148-164.
125. TuszynskiMH,Roberts J, Senut MC,UHS, GageFH(1996) Gene therapy in the adult primate brain: Intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Therapy 3, 305-314.
126. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med 15, 331-337.
127. Diniz BS, Teixeira AL (2011) Brain-derived neurotrophic factor and Alzheimer's disease: Physiopathology and beyond. Neuromolecular Med 13, 217-222.
128. Fjord-Larsen L, Kusk P, Tornøe J, Juliusson B, Torp M, Bjarkam CR, Nielsen MS, Handberg A, Sørensen JC, Wahlberg LU (2010) Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain. Mol Ther 18, 2164-2172.
129. Eriksdotter-Jönhagen M, Linderoth B, Lind G, Aladellie L, Almkvist O, Andreasen N, Blennow K, Bogdanovic N, Jelic V, Kadir A, Nordberg A, Sundström E, Wahlund LO, Wall A,WibergM,Winblad B, Seiger A, Almqvist P,Wahlberg L (2012) Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease. Dement Geriatr Cogn Disord 33, 18-28.
130. Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, Doege C, Chau L, Aubry L, Vanti WB, Moreno H, AbeliovichA (2011) Directed conversion of Alzheimer's disease patient skin fibroblasts into functional neurons. Cell 146, 359-371.
131. Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, Carson CT, Laurent LC, Marsala M, Gage FH, Remes AM, Koo EH, Goldstein LS (2012) Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 482, 216-220.
132. Jankovic J (2008) Parkinson's disease: Clinical features and diagnosis. J Neurol Neurosurg Psychiatr 79, 368-376.
133. Samii A, Nutt JG, Ransom BR (2004) Parkinson's disease. Lancet 363, 1783-1793.
134. Davie CA (2008) A review of Parkinson's disease. Br Med Bull 86, 109-127.
135. GalpernWR,LangAE(2006) Interface between tauopathies and synucleinopathies: A tale of two proteins. Ann Neurol 59, 449-458.
136. Aarsland D, Londos E, Ballard C (2009) Parkinson's disease dementia and dementia with Lewy bodies: Different aspects of one entity. Int Psychogeriatr 21, 216-219.
137. Lindvall O, Rehncrona S, Brundin P, Gustavii B, Astedt B, Widner H, Lindholm T, Björklund A, Leenders KL, Rothwell JC, Frackowiak R, Marsden D, Johnels B, Steg G, Freedman R, Hoffer BJ, Seiger A, Bygdeman M, Strömberg I, Olson L (1989) Human fetal dopamine neurons grafted into the striatum in two patients with Parkinson's disease: A detailed account of methodology and 16 month followup. Arch Neurol 46, 615-631.
138. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S,Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 344, 710-719.
139. Munchau A, Bhatia K (2000) Pharmacological treatment of Parkinson's disease. Postgrad Med J 76, 602-610.
140. Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, Lashley T, Quinn NP, Rehncrona S, Björklund A, Widner H, Revesz T, Lindvall O, Brundin P (2008) Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 14, 501-503.
141. Kordower JH, ChuY, Hauser RA, Freeman TB, OlanowCW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 14, 504- 506.
142. Mendez I, Viñuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski JQ, IsacsonO(2008) Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med 14, 507-509.
143. Ĺevesque MF, Neuman T, Rezak M (2009) Therapeutic microinjection of autologous adult human neural stem cells and differentiated neurons for Parkinson's disease: Five-year post-operative outcome. Open Stem Cell J 1, 20-29.
144. Li Y, Chen J, Wang L, Zhang L, Lu M, Chopp M (2001) 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 316, 67-70.
145. Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A 105, 5856-5861.
146. Redmond DE, Jr., Bjugstad KB, Teng YD, Ourednik V, Ourednik J,Wakeman DR, Parsons XH, Gonzalez R, Blanchard BC, Kim SU, Gu Z, Lipton SA, Markakis EA, Roth RH, Elsworth JD, Sladek JR Jr, Sidman RL, Snyder EY (2007) Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Proc Natl Acad Sci U S A 104, 12175-12180.
147. Yasuhara T, Matsukawa N, Hara K, Yu G, Xu L, Maki M, Kim SU, Borlongan CV (2006) Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson's disease. J Neurosci 26, 12497-12511.
148. Bjorklund LM, Śanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A 99, 2344-2349.
149. Kim JH, Auerbach JM, Rodŕiguez-Ǵomez JA, Velasco I, Gavin D, LumelskyN, Lee SH, Nguyen J, Śanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418, 50-56.
150. TakagiY, Nishimura M, Morizane A,Takahashi J, Nozaki K, Hayashi J, Hashimoto N (2005) Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain. J Neurosurg 103, 304- 310.
151. Brederlau A, Correia AS, Anisimov SV, Elmi M, Paul G, Roybon L, Morizane A, Bergquist F, Riebe I, Nannmark U, Carta M, Hanse E, Takahashi J, Sasai Y, Funa K, Brundin P, Eriksson PS, Li JY (2006) Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: Effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells 24, 1433-1440.
152. Rodŕiguez-Ǵomez JA, Lu JQ, Velasco I, Rivera S, Zoghbi SS, Liow JS, Musachio JL, Chin FT, Toyama H, Seidel J, Green MV, Thanos PK, Ichise M, Pike VW, Innis RB, McKay RD (2007) Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of Parkinson disease. Stem Cells 25, 918-928.
153. Cho MS, Lee YE, Kim JY, Chung S, Cho YH, Kim DS, Kang SM, Lee H, Kim MH, Kim JH, Leem JW, Oh SK, Choi YM, Hwang DY, Chang JW, Kim DW (2008) Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 105, 3392-3397.
154. Thinyane K, Baier PC, Schindehütte J, Mansouri A, Paulus W, Trenkwalder C, Flügge G, Fuchs E (2005) Fate of predifferentiated mouse embryonic stem cells transplanted in unilaterally 6-hydroxydopamine lesioned rats: Histological characterization of the grafted cells. Brain Res 1045, 80-87.
155. Ohmachi S, Watanabe Y, Mikami T, Kusu N, Ibi T, Akaike A, Itoh N (2000) FGF-20, a novel neurotrophic factor, preferentially expressed in the substantia nigra pars compacta of rat brain. Biochem Biophys Res Commun 277, 355-360.
156. Ohmachi S, Mikami T, Konishi M, Miyake A, Itoh N (2003) Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c. J Neurosci Res 72, 436-443.
157. Murase S, McKay RD (2006) A specific survival response in dopamine neurons at most risk in Parkinson's disease. J Neurosci 26, 9750-9760.
158. Sleeman IJ, Boshoff EL, Duty S (2012) Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson' disease. Neuropharmacology 63, 1268-1277.
159. Winkler C, Sauer H, Lee CS, Bjorklund A (1996) ShorttermGDNFtreatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease. J Neurosci 16, 7206-7215.
160. Rosenblad C, Kirik D, Devaux B, Moffat B, Phillips HS, Björklund A (1999) Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle. Eur J Neurosci 11, 1554- 1556.
161. Kirik D, Rosenblad C, Björklund A (1998) Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp Neurol 152, 259-277.
162. Gill SS, Patel NK, Hotton GR, O'Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 9, 589-595.
163. Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, YoungB(2005) Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 102, 216-222.
164. Akerud P, Canals JM, Snyder EY, Arenas E (2001) Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson's disease. J Neurosci 21, 8108-8118.
165. Moloney TC, Rooney GE, Barry FP, Howard L, Dowd E (2010) Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain. Brain Res 1359, 33-43.
166. Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symp toms of rats with Parkinson's disease. Proc Natl Acad Sci U S A 105, 5856-5861.
167. Rhee YH, Ko JY, Chang MY, Yi SH, Kim D, Kim CH, Shim JW, Jo AY, Kim BW, Lee H, Lee SH, Suh W, Park CH, Koh HC, Lee YS, Lanza R, Kim KS, Lee SH (2011) Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest 121, 2326-2335.
168. Chen LW, Kuang F, Wei LC, Ding YX, Yung KK, Chan YS (2011) Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease. CNS Neurol Disord Drug Targets 10, 449-458.
169. Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, Yow A, Soldner F, Hockemeyer D, Hallett PJ, Osborn T, Jaenisch R, Isacson O (2010) Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci U S A 107, 15921-15926.
170. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D (2006) Human umbilical cord matrix stem cells: Preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells 24, 781-792.
171. Lu L, Zhao C, Liu Y, Sun X, Duan C, Ji M, Zhao H, Xu Q, Yang (2005) Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease. Brain Res Protoc 15, 46-51.
172. Wu QY, Li J, Feng ZT, Wang TH (2007) Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimer's disease rat model. Neurosci Lett 417, 281-285.