Functional multipotency of stem cells: A conceptual review of neurotrophic factor-based evidence and its role in translational research

Current Neuropharmacology

Volumn 9, Issue 4, 2011, Pages 574-585

  Teng, Yang D ^a,b,c   Yu, Dou ^b   Ropper, Alexander E ^b   Li, Jianxue ^d   Kabatas, Serdar ^b   Wakeman, Dustin R ^e   Wang, Junmei ^b   Sullivan, Maryrose P ^f   Eugene Redmond Jr , D ^g   Langer, Robert ^h   Snyder, Evan Y ^e   Sidman, Richard L ^d  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c and Red Sox Foundation and Massachusetts General Hospital Home Base Program   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e BURNHAM INSTITUTE   (United States)

^f BRIGHAM AND WOMEN S HOSPITAL   (United States)

^g YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h Massachusetts Institute of Technology Cambridge   (United States)

Author keywords

Multipotency; Neural Repair; Neural stem cells; Neurotrophic factors; Spinal Cord Injury; Stem cells

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; NERVE GROWTH FACTOR; NEUROTROPHIC FACTOR; NEUROTROPHIN 3; NEUROTROPHIN 4;

ALZHEIMER DISEASE; DEGENERATIVE DISEASE; DEVELOPMENTAL STAGE; EPIGENETICS; GENETIC ENGINEERING; HUMAN; MICROENVIRONMENT; NEURAL STEM CELL; NONHUMAN; PLURIPOTENT STEM CELL; REVIEW; SPINAL CORD INJURY; SPINAL CORD REGENERATION; TRANSGENE; TRANSLATIONAL RESEARCH;

EID: 82955220539     PISSN: 1570159X     EISSN: 18756190     Source Type: Journal    
DOI: 10.2174/157015911798376299     Document Type: Review

References (186)

1. Gage, F.H. Stem cells of the central nervous system. Curr. Opin. Neurobiol., 1998, 8(5), 671-676.
2. Ryder, E.F.; Snyder, E.Y.; Cepko, C.L. Establishment and characterization of multipotent neural cell lines using retrovirus vectormediated oncogene transfer. J. Neurobiol., 1990, 21(2), 356-375.
3. Reynolds, B.A.; Weiss, S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992, 255(5052), 1707-1710.
4. Snyder, E.Y.; Deitcher, D.L.; Walsh, C.; Arnold-Aldea, S.; Hartwieg, E.A.; Cepko, C.L. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell, 1992, 68(1), 33-51.
5. Angevine, J.B., Jr.; Sidman, R.L. Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse. Nature., 1961, 192, 766-768.
6. Altman, J. Are new neurons formed in the brains of adult mammals? Science, 1962, 135, 1127-1128.
7. Teng, Y.D.; Kabatas, S.; Wakeman, D.R.; Li, J.; Snyder, E.Y.; Sidman, R.L. Functional multipotency of neural stem cells and its therapeutic implications. In: Perspectives of Stem Cells: From tools for studying mechanisms of neuronal differentiation towards therapy. Ulrich, H. Ed.; Springer-Verlag Inc.: San Diego, 2009; Chapter 16: pp. 255-270.
8. Jäderstad, J.; Jäderstad, L.M.; Li, J.; Chintawar, S.; Salto, C.; Pandolfo, M.; Ourednik, V.; Teng, Y.D.; Sidman, R.L.; Arenas, E.; Snyder, E.Y.; Herlenius, E. Communication via gap junctions underlies early functional and beneficial interactions between grafted neural stem cells and the host. Proc. Natl. Acad. Sci. USA, 2010, 107(11), 5184-5189.
9. Rosario, C.M.; Yandava, B.D.; Kosaras, B.; Zurakowski, D.; Sidman, R.L.; Snyder, E.Y. Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action. Development, 1997, 124(21), 4213-4224.
10. Auerbach, J.M.; Eiden, M.V.; McKay, R.D. Transplanted CNS stem cells form functional synapses in vivo. Eur. J. Neurosci., 2000, 12(5), 1696-1704.
11. Chung, S.; Shin, B.S.; Hwang, M.; Lardaro, T.; Kang, U.J.; Isacson, O.; Kim, K.S. Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitro. Stem Cells, 2006, 24(6), 1583-1593.
12. Yandava, B.D.; Billinghurst, L.L.; Snyder, E.Y. "Global" cell replacement is feasible via neural stem Cell Transplant. ation: evidence from the dysmyelinated shiverer mouse brain. Proc. Natl. Acad. Sci. USA, 1999, 96(12), 7029-7034.
13. Imitola, J.; Raddassi, K.; Park, K.I.; Mueller, F.J.; Nieto, M.; Teng, Y.D.; Frenkel, D.; Li, J.; Sidman, R.L.; Walsh, C.A.; Snyder, E.Y.; Khoury, S.J. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc. Natl. Acad. Sci. USA, 2004, 101(52), 18117-18122.
14. Redmond, D.E., Jr.; Bjugstad, K.B.; Teng, Y.D.; Ourednik, V.; Ourednik, J.; Wakeman, D.R.; Parsons, X.H.; Gonzalez, R.; Blanchard, B.C.; Kim, S.U.; Gu, Z.; Lipton, S.A.; Markakis, E.A.; Roth, R.H.; Elsworth, J.D.; Sladek, J.R., Jr.; Sidman, R.L.; Snyder, E.Y. Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Proc. Natl. Acad. Sci. USA, 2007, 104(29), 12175 12180.
15. Behrstock, S.; Ebert, A.D.; Klein, S.; Schmitt, M.; Moore, J.M.; Svendsen, C.N. Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF. Cell Transplant., 2008, 17(7), 753-762.
16. Aboody, K.S.; Brown, A.; Rainov, N.G.; Bower, K.A.; Liu, S.; Yang, W.; Small, J.E.; Herrlinger, U.; Ourednik, V.; Black, P.M.; Breakefield, X.O.; Snyder, E.Y. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc. Natl. Acad. Sci. USA, 2000, 97(23), 12846-12851.
17. Park, K.I.; Teng, Y.D.; Snyder, E.Y. The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat. Biotechnol., 2002, 20(11), 1111-1117.
18. Ma, D.K.; Ming, G.L.; Song, H. Glial influences on neural stem cell development: cellular niches for adult neurogenesis. Curr. Opin. Neurobiol., 2005, 15(5), 514-520.
19. Cao, Q.L.; Zhang, Y.P.; Howard, R.M.; Walters, W.M.; Tsoulfas, P.; Whittemore, S.R. Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage. Exp. Neurol., 2001, 167(1), 48-58.
20. Teng, Y.D.; Lavik, E.B.; Qu, X.; Park, K.I.; Ourednik, J.; Zurakowski, D.; Langer, R.; Snyder, E.Y. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc. Natl. Acad. Sci. USA, 2002, 99(5), 3024-3029.
21. Pluchino, S.; Zanotti, L.; Rossi, B.; Brambilla, E.; Ottoboni, L.; Salani, G.; Martinello, M.; Cattalini, A.; Bergami, A.; Furlan, R.; Comi, G.; Constantin, G.; Martino, G. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature, 2005, 436(7048), 266-271.
22. Gersh, B.J.; Simari, R.D.; Behfar, A.; Terzic, C.M.; Terzic, A. Cardiac cell repair therapy: a clinical perspective. Mayo Clin. Proc., 2009, 84(10), 876-892.
23. Redmond, D.E., Jr.; Elsworth, J.D.; Roth, R.H.; Leranth, C.; Collier, T.J.; Blanchard, B.; Bjugstad, K.B.; Samulski, R.J.; Aebischer, P.; Sladek, J.R., Jr. Embryonic substantia nigra grafts in the mesencephalon send neurites to the host striatum in non-human primate after overexpression of GDNF. J. Comp. Neurol., 2009, 515(1), 31-40.
24. Mocchetti, I.; Bachis, A.; Masliah, E. Chemokine receptors and neurotrophic factors: potential therapy against aids dementia? J. Neurosci. Res., 2008, 86(2), 243-255.
25. Ventura, C.; Cavallini, C.; Bianchi, F.; Cantoni, S. Stem cells and cardiovascular repair: a role for natural and synthetic molecules harboring differentiating and paracrine logics. Cardiovasc. Hematol. Agents Med. Chem., 2008, 6(1), 60-68.
26. Kaplan, D.R.; Miller, F.D. Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol., 2000, 10(3), 381-391.
27. Aicardi, G.; Argilli, E.; Cappello, S.; Santi, S.; Riccio, M.; Thoenen, H.; Canossa, M. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor. Proc. Natl. Acad. Sci. USA, 2004, 101(44), 15788-15792.
28. Tuszynski, M.H. Neurotrophic factors. In: CNS Regeneration: Basic Science and Clinical Advances. Tuszynski, J.H. Ed.; Academic Press: San Diego: 1999; pp 109-158.
29. Tuszynski, M.H. Nerve growth factor gene delivery: animal models to clinical trials. Dev. Neurobiol., 2007, 67(9), 1204-1215.
30. Bibel, M.; Barde, Y.A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev., 2000, 14(23), 2919-2937.
31. Hapner, S.J.; Boeshore, K.L.; Large, T.H.; Lefcort, F. Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR). Dev. Biol., 1998, 201(1), 90-100.
32. Guo, J.S.; Zeng, Y.S.; Li, H.B.; Huang, W.L.; Liu, R.Y.; Li, X.B.; Ding, Y.; Wu, L.Z.; Cai, D.Z. Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury. Spinal Cord, 2007, 45(1), 15-24.
33. Wang, J.M.; Zeng, Y.S.; Liu, R.Y.; Huang, W.L.; Xiong, Y.; Wang, Y.H.; Chen, S.J.; Teng, Y.D. Recombinant adenovirus vector-mediated functional expression of neurotropin-3 receptor (TrkC) in neural stem cells. Exp. Neurol., 2007, 203(1), 123-127.
34. Castellanos, D.A.; Tsoulfas, P.; Frydel, B.R.; Gajavelli, S.; Bes, J.C.; Sagen, J. TrkC overexpression enhances survival and migration of neural stem Cell Transplant. s in the rat spinal cord. Cell Transplant., 2002, 11(3), 297-307.
35. Bartkowska, K.; Paquin, A.; Gauthier, A.S.; Kaplan, D.R.; Miller, F.D. Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development. Development., 2007, 134(24), 4369-4380.
36. Barker, P.A.; Lomen-Hoerth, C.; Gensch, E.M.; Meakin, S.O.; Glass, D.J.; Shooter, E.M. Tissue-specific alternative splicing generates two isoforms of the trkA receptor. J. Biol. Chem., 1993, 268(20), 15150-15157.
37. Tacconelli, A.; Farina, A.R.; Cappabianca, L.; Desantis, G.; Tessitore, A.; Vetuschi, A.; Sferra, R.; Rucci, N.; Argenti, B.; Screpanti, I.; Gulino, A.; Mackay, A.R. TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell, 2004, 6(4), 347-360.
38. Narumiya, S.; Ohno, M.; Tanaka, N.; Yamano, T.; Shimada, M. Enhanced expression of full-length TrkB receptors in young rat brain with hypoxic/ischemic injury. Brain Res., 1998, 797(2), 278-286.
39. Fryer, R.H.; Kaplan, D.R.; Kromer, L.F. Truncated trkB receptors on nonneuronal cells inhibit BDNF-induced neurite outgrowth in vitro. Exp. Neurol., 1997, 148(2), 616-627.
40. Bartkowska, K.; Paquin, A.; Gauthier, A.S.; Kaplan, D.R.; Miller, F.D. Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development. Development., 2007, 134(24), 4369-4380.
41. Hempstead, B.L. The many faces of p75NTR. Curr. Opin. Neurobiol., 2002, 12(3), 260-267.
42. Islam, O.; Loo, T.X.; Heese, K. Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling pathways. Curr. Neurovasc. Res., 2009, 6(1), 42-53.
43. Naumann, T.; Casademunt, E.; Hollerbach, E.; Hofmann, J.; Dechant, G.; Frotscher, M.; Barde, Y.A. Complete deletion of the neurotrophin receptor p75NTR leads to long-lasting increases in the number of basal forebrain cholinergic neurons. J. Neurosci., 2002, 22(7), 2409-2418.
44. Troy, C.M.; Friedman, J.E.; Friedman, W.J. Mechanisms of p75 mediated death of hippocampal neurons. Role of caspases. J. Biol. Chem., 2002, 277(37), 34295-34302.
45. Moscatelli, I.; Pierantozzi, E.; Camaioni, A.; Siracusa, G.; Campagnolo, L. p75 neurotrophin receptor is involved in proliferation of undifferentiated mouse embryonic stem cells. Exp. Cell Res., 2009, 315(18), 3220-3232.
46. Zhang, W.; Zeng, Y.S.; Wang, J.M.; Ding, Y.; Li, Y.; Wu, W. Neurotrophin-3 improves retinoic acid-induced neural differentiation of skin-derived precursors through a p75NTR-dependent signaling pathway. Neurosci. Res., 2009, 64(2), 170-176.
47. Morris, Z.S.; McClatchey, A.I. The neurofibroma cell of origin: SKPs expand the playing field. Cell Stem Cell, 2009, 4(5), 371-372.
48. Reier, P.J. Cellular transplantation strategies for spinal cord injury and translational neurobiology. NeuroRx, 2004, 1(4), 424-451.
49. Fitch, M.T.; Silver, J. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol., 2008, 209(2), 294-301.
50. Terenghi, G. Peripheral nerve regeneration and neurotrophic factors. J. Anat., 1999, 194 (Pt 1), 1-14.
51. Boyd, J.G.; Gordon, T. Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury. Mol. Neurobiol., 2003, 27(3), 277-324.
52. Silver, J.; Miller, J.H. Regeneration beyond the glial scar. Nat. Rev. Neurosci., 2004, 5(2), 146-156.
53. Fawcett, J.W. Overcoming inhibition in the damaged spinal cord. J. Neurotrauma, 2006, 23(3-4), 371-383.
54. Neumann, S.; Woolf, C.J. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron, 1999, 23(1), 83-91.
55. Seijffers, R.; Mills, C.D.; Woolf, C.J. ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. J. Neurosci., 2007, 27(30), 7911-7920.
56. Lakatos, A.; Franklin, R.J. Transplant mediated repair of the central nervous system: an imminent solution? Curr. Opin. Neurol., 2002, 15(6), 701-705.
57. Tuszynski, M.H. Growth-factor gene therapy for neurodegenerative disorders. Lancet Neurol., 2002, 1(1), 51-57.
58. Qiu, J.; Cai, D.; Dai, H.; McAtee, M.; Hoffman, P.N.; Bregman, B.S.; Filbin, M.T. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron, 2002, 34(6), 895-903.
59. Novikova, L.N.; Novikov, L.N.; Kellerth, J.O. Biopolymers and biodegradable smart implants for tissue regeneration after spinal cord injury. Curr. Opin. Neurol., 2003, 16(6), 711-715.
60. Rossi, F.; Gianola, S.; Corvetti, L. Regulation of intrinsic neuronal properties for axon growth and regeneration. Prog. Neurobiol., 2007, 81(1), 1-28.
61. Lu, P.; Yang, H.; Jones, L.L.; Filbin, M.T.; Tuszynski, M.H. Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. J. Neurosci., 2004, 24(28), 6402-6409.
62. Nikulina, E.; Tidwell, J.L.; Dai, H.N.; Bregman, B.S.; Filbin, M.T. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc. Natl. Acad. Sci. USA, 2004, 101(23), 8786-8790.
63. Pearse, D.D.; Pereira, F.C.; Marcillo, A.E.; Bates, M.L.; Berrocal, Y.A.; Filbin, M.T.; Bunge, M.B. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat. Med., 2004, 10(6), 610-616.
64. Kobayashi, N.R.; Fan, D.P.; Giehl, K.M.; Bedard, A.M.; Wiegand, S.J.; Tetzlaff, W. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1 tubulin mRNA expression, and promote axonal regeneration. J. Neurosci., 1997, 17(24), 9583-9595.
65. Liu, Y.; Kim, D.; Himes, B.T.; Chow, S.Y.; Schallert, T.; Murray, M.; Tessler, A.; Fischer, I. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J. Neurosci., 1999, 19(11), 4370-4387.
66. Jin, Y.; Fischer, I.; Tessler, A.; Houle, J.D. Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp. Neurol., 2002, 177(1), 265-275.
67. Kwon, B.K.; Liu, J.; Messerer, C.; Kobayashi, N.R.; McGraw, J.; Oschipok, L.; Tetzlaff, W. Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc. Natl. Acad. Sci. USA, 2002, 99(5), 3246-3251.
68. Lu, P.; Blesch, A.; Tuszynski, M.H. Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons. J. Comp. Neurol., 2001, 436(4), 456-470.
69. Schnell, L.; Schneider, R.; Kolbeck, R.; Barde, Y.A.; Schwab, M.E. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature., 1994, 367(6459), 170-173.
70. Grill, R.; Murai, K.; Blesch, A.; Gage, F.H.; Tuszynski, M.H. Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J. Neurosci., 1997, 17(14), 5560-5572.
71. Kadoya, K.; Tsukada, S.; Lu, P.; Coppola, G.; Geschwind, D.; Filbin, M.T.; Blesch, A.; Tuszynski, M.H. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron, 2009, 64(2), 165-172.
72. Hendriks, W.T.; Ruitenberg, M.J.; Blits, B.; Boer, G.J.; Verhaagen, J. Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord. Prog. Brain Res., 2004, 146, 451-476.
73. Ying, Z.; Roy, R.R.; Zhong, H.; Zdunowski, S.; Edgerton, V.R.; Gomez-Pinilla, F. BDNF-exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats. Neuro Science, 2008, 155(4), 1070-1078.
74. Konya, D.; Liao, W.L.; Choi, H.; Yu, D.; Woodard, M.C.; Newton, K.M.; King, A.M.; Pamir, N.M.; Black, P.M.; Frontera, W.R.; Sabharwal, S.; Teng, Y.D. Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity. Regen. Med., 2008, 3(3), 309-327.
75. Foret, A.; Quertainmont, R.; Botman, O.; Bouhy, D.; Amabili, P.; Brook, G.; Schoenen, J.; Franzen, R. Stem cells in the adult rat spinal cord: plasticity after injury and treadmill training exercise. J. Neurochem., 2010, 112(3), 762-772.
76. Behrman, A.L.; Bowden, M.G.; Nair, P.M. Neuroplasticity after spinal cord injury and training: an emerging paradigm shift in rehabilitation and walking recovery. Phys. Ther., 2006, 86(10), 1406 1425.
77. Mocchetti, I.; Brown, M. Targeting neurotrophin receptors in the central nervous system. CNS Neurol. Disord. Drug Targets, 2008, 7(1), 71-82.
78. Adrian, E.K.; Jr.; Walker, B.E. Incorporation of thymidine-H3 by cells in normal and injured mouse spinal cord. J. Neuropathol. Exp. Neurol., 1962, 21, 597-609.
79. Weiss, S.; Dunne, C.; Hewson, J.; Wohl, C.; Wheatley, M.; Peterson, A.C.; Reynolds, B.A. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci., 1996, 16(23), 7599-7609.
80. Tramontin, A.D.; Garcia-Verdugo, J.M.; Lim, D.A.; Alvarez Buylla, A. Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment. Cereb. Cortex, 2003, 13(6), 580-587.
81. Shihabuddin, L.S.; Horner, P.J.; Ray, J.; Gage, F.H. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J. Neurosci., 2000, 20(23), 8727-8735.
82. Horner, P.J.; Power, A.E.; Kempermann, G.; Kuhn, H.G.; Palmer, T.D.; Winkler, J.; Thal, L.J.; Gage, F.H. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J. Neurosci., 2000, 20(6), 2218-2228.
83. Song, H.J.; Stevens, C.F.; Gage, F.H. Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat. Neurosci., 2002, 5(5), 438-445.
84. Frisen, J.; Johansson, C.B.; Torok, C.; Risling, M.; Lendahl, U. Rapid, widespread, and longlasting induction of nestin contributes to the generation of glial scar tissue after CNS injury. J. Cell Biol., 1995, 131(2), 453-464.
85. Shihabuddin, L.S.; Palmer, T.D.; Gage, F.H. The search for neural progenitor cells: prospects for the therapy of neurodegenerative disease. Mol. Med. Today, 1999, 5(11), 474-480.
86. Yamamoto, S.; Yamamoto, N.; Kitamura, T.; Nakamura, K.; Nakafuku, M. Proliferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord. Exp. Neurol., 2001, 172(1), 115-127.
87. Matthews, M.A.; St Onge, M.F.; Faciane, C.L. An electron microscopic analysis of abnormal ependymal cell proliferation and envelopment of sprouting axons following spinal cord transection in the rat. Acta Neuropathol., 1979, 45(1), 27-36.
88. Tripathi, R.B.; McTigue, D.M. Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats. J. Comp. Neurol., 2008, 510(2), 129-144.
89. Takahashi, M.; Arai, Y.; Kurosawa, H.; Sueyoshi, N.; Shirai, S. Ependymal cell reactions in spinal cord segments after compression injury in adult rat. J. Neuropathol. Exp. Neurol., 2003, 62(2), 185 194.
90. McTigue, D.M.; Horner, P.J.; Stokes, B.T.; Gage, F.H. Neurotrophin 3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J. Neurosci., 1998, 18(14), 5354-5365.
91. Mothe, A.J.; Tator, C.H. Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. NeuroScience, 2005, 131(1), 177-187.
92. Kempermann, G.; Kuhn, H.G.; Gage, F.H. More hippocampal neurons in adult mice living in an enriched environment. Nature, 1997, 386(6624), 493-495.
93. Teng, Y.D.; Liao, W.L.; Choi, H.; Konya, D.; Sabharwal, S.; Langer, R.; Sidman, R.L.; Snyder, E.Y.; Frontera, W.R. Physical activity-mediated functional recovery after spinal cord injury: potential roles of neural stem cells. Regen. Med., 2006, 1(6), 763-776.
94. Gomez-Pinilla, F.; Ying, Z.; Roy, R.R.; Molteni, R.; Edgerton, V.R. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J. Neurophysiol., 2002, 88(5), 2187 2195.
95. Jakeman, L.B.; Wei, P.; Guan, Z.; Stokes, B.T. Brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cho linergic fibers after spinal cord injury. Exp. Neurol., 1998, 154(1), 170-184.
96. Ying, Z.; Roy, R.R.; Edgerton, V.R.; Gomez-Pinilla, F. Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord. Brain Res., 2003, 987(1), 93-99.
97. Danzer, S.C.; He, X.; McNamara, J.O. Ontogeny of seizureinduced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus. Hippocampus, 2004, 14(3), 345 355.
98. Osaka, M.; Honmou, O.; Murakami, T.; Nonaka, T.; Houkin, K.; Hamada, H.; Kocsis, J.D. Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome. Brain Res., 2010, 1343, 226-235.
99. van Praag, H.; Kempermann, G.; Gage, F.H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci., 1999, 2(3), 266-270.
100. van Praag, H.; Christie, B.R.; Sejnowski, T.J.; Gage, F.H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl. Acad. Sci. USA, 1999, 96(23), 13427-13431.
101. Vaynman, S.; Gomez-Pinilla, F. License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil. Neural Repair, 2005, 19(4), 283-295.
102. Krityakiarana, W.; Espinosa-Jeffrey, A.; Ghiani, C.A.; Zhao, P.M.; Topaldjikian, N.; Gomez-Pinilla, F.; Yamaguchi, M.; Kotchabhakdi, N.; de Vellis, J. Voluntary exercise increases oligodendrogenesis in spinal cord. Int. J. Neurosci., 2010, 120(4), 280-290.
103. Snyder, E.Y.; Taylor, R.M.; Wolfe, J.H. Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature, 1995, 374(6520), 367-370.
104. Imitola, J.; Park, K.I.; Teng, Y.D.; Nisim, S.; Lachyankar, M.; Ourednik, J.; Mueller, F.J.; Yiou, R.; Atala, A.; Sidman, R.L.; Tuszynski, M.; Khoury, S.J.; Snyder, E.Y. Stem cells: cross-talk and developmental programs. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2004, 359(1445), 823-837.
105. Flax, J.D.; Aurora, S.; Yang, C.; Simonin, C.; Wills, A.M.; Billinghurst, L.L.; Jendoubi, M.; Sidman, R.L.; Wolfe, J.H.; Kim, S.U.; Snyder, E.Y. Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat. Biotechnol., 1998, 16(11), 1033-1039.
106. Hill, C.E.; Guller, Y.; Raffa, S.J.; Hurtado, A.; Bunge, M. A calpain inhibitor enhances the survival of Schwann cells in vitro and after transplantation into the injured spinal cord. J. Neurotrauma, 2010, 27(9), 1685-1695.
107. Yu, D.; Neeley, W.L.; Pritchard, C.D.; Slotkin, J.R.; Woodard, E.J.; Langer, R.; Teng, Y.D. Blockade of peroxynitrite-induced neural stem cell death in the acutely injured spinal cord by drugreleasing polymer. Stem Cells, 2009, 27(5), 1212-1222.
108. Hedlund, E.; Hefferan, M.P.; Marsala, M.; Isacson, O. Cell therapy and stem cells in animal models of motor neuron disorders. Eur. J. Neurosci., 2007, 26(7), 1721-1737.
109. Suzuki, M.; Svendsen, C.N. Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis. Trends Neurosci., 2008, 31(4), 192-198.
110. Lu, P.; Jones, L.L.; Snyder, E.Y.; Tuszynski, M.H. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp. Neurol., 2003, 181(2), 115-129.
111. Levi-Montalcini, R. The nerve growth factor 35 years later. Science, 1987, 237(4819), 1154-1162.
112. Levi-Montalcini, R.; Hamburger, V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J. Exp. Zool., 1951, 116(2), 321-361.
113. Fischer, W.; Wictorin, K.; Bjorklund, A.; Williams, L.R.; Varon, S.; Gage, F.H. Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature, 1987, 329(6134), 65-68.
114. Markowska, A.L.; Koliatsos, V.E.; Breckler, S.J.; Price, D.L.; Olton, D.S. Human nerve growth factor improves spatial memory in aged but not in young rats. J. Neurosci., 1994, 14(8), 4815-4824.
115. Bezprozvanny, I.; Mattson, M.P. Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci., 2008, 31(9), 454-463.
116. Koliatsos, V.E.; Clatterbuck, R.E.; Nauta, H.J.; Knusel, B.; Burton, L.E.; Hefti, F.F.; Mobley, W.C.; Price, D.L. Human nerve growth factor prevents degeneration of basal forebrain cholinergic neurons in primates. Ann. Neurol., 1991, 30(6), 831-840.
117. Emerich, D.F.; Winn, S.R.; Harper, J.; Hammang, J.P.; Baetge, E.E.; Kordower, J.H. Implants of polymer-encapsulated human NGF-secreting cells in the nonhuman primate: rescue and sprouting of degenerating cholinergic basal forebrain neurons. J. Comp. Neurol., 1994, 349(1), 148-164.
118. Kordower, J.H.; Winn, S.R.; Liu, Y.T.; Mufson, E.J.; Sladek, J.R., Jr.; Hammang, J.P.; Baetge, E.E.; Emerich, D.F. The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. Proc. Natl. Acad. Sci. USA, 1994, 91(23), 10898 10902.
119. Holtzman, D.M.; Li, Y.; Parada, L.F.; Kinsman, S.; Chen, C.K.; Valletta, J.S.; Zhou, J.; Long, J.B.; Mobley, W.C. p140trk mRNA marks NGF-responsive forebrain neurons: evidence that trk gene expression is induced by NGF. Neuron, 1992, 9(3), 465-478.
120. Tuszynski, M.H.; Gage, F.H. Bridging grafts and transient nerve growth factor infusions promote long-term central nervous system neuronal rescue and partial functional recovery. Proc. Natl. Acad. Sci. USA, 1995, 92(10), 4621-4625.
121. Cooper, J.D.; Salehi, A.; Delcroix, J.D.; Howe, C.L.; Belichenko, P.V.; Chua-Couzens, J.; Kilbridge, J.F.; Carlson, E.J.; Epstein, C.J.; Mobley, W.C. Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc. Natl. Acad. Sci. USA, 2001, 98(18), 10439-10444.
122. Tuszynski, M.H.; Roberts, J.; Senut, M.C.; U, H.S.; Gage, F.H. Gene therapy in the adult primate brain: intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Ther., 1996, 3(4), 305-314.
123. Perry, E.K.; Curtis, M.; Dick, D.J.; Candy, J.M.; Atack, J.R.; Bloxham, C.A.; Blessed, G.; Fairbairn, A.; Tomlinson, B.E.; Perry, R.H. Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry, 1985, 48(5), 413-421.
124. Perry, E.K.; Tomlinson, B.E.; Blessed, G.; Bergmann, K.; Gibson, P.H.; Perry, R.H. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br. Med. J., 1978, 2(6150), 1457-1459.
125. Candy, J.M.; Perry, R.H.; Perry, E.K.; Irving, D.; Blessed, G.; Fairbairn, A.F.; Tomlinson, B.E. Pathological changes in the nucleus of Meynert in Alzheimer's and Parkinson's diseases. J. Neurol. Sci., 1983, 59(2), 277-289.
126. Masliah, E.; Terry, R.D.; Alford, M.; DeTeresa, R.; Hansen, L.A. Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease. Am. J. Pathol., 1991, 138(1), 235 246.
127. Mufson, E.J.; Ikonomovic, M.D.; Styren, S.D.; Counts, S.E.; Wuu, J.; Leurgans, S.; Bennett, D.A.; Cochran, E.J.; DeKosky, S.T. Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease. Arch. Neurol., 2003, 60(8), 1143-1148.
128. Korsching, S.; Auburger, G.; Heumann, R.; Scott, J.; Thoenen, H. Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J., 1985, 4(6), 1389-1393.
129. Whittemore, S.R.; Ebendal, T.; Larkfors, L.; Olson, L.; Seiger, A.; Stromberg, I.; Persson, H. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. Proc. Natl. Acad. Sci. USA, 1986, 83(3), 817-821.
130. Savaskan, E.; Muller-Spahn, F.; Olivieri, G.; Bruttel, S.; Otten, U.; Rosenberg, C.; Hulette, C.; Hock, C. Alterations in trk A, trk B and trk C receptor immunoreactivities in parietal cortex and cerebellum in Alzheimer's disease. Eur. Neurol., 2000, 44(3), 172-180.
131. Chu, Y.; Cochran, E.J.; Bennett, D.A.; Mufson, E.J.; Kordower, J.H. Down-regulation of trkA mRNA within nucleus basalis neurons in individuals with mild cognitive impairment and Alzheimer's disease. J. Comp. Neurol., 2001, 437(3), 296-307.
132. Mufson, E.J.; Ma, S.Y.; Dills, J.; Cochran, E.J.; Leurgans, S.; Wuu, J.; Bennett, D.A.; Jaffar, S.; Gilmor, M.L.; Levey, A.I.; Kordower, J.H. Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease. J. Comp. Neurol., 2002, 443(2), 136-153.
133. Salehi, A.; Delcroix, J.D.; Belichenko, P.V.; Zhan, K.; Wu, C.; Valletta, J.S.; Takimoto-Kimura, R.; Kleschevnikov, A.M.; Sambamurti, K.; Chung, P.P.; Xia, W.; Villar, A.; Campbell, W.A.; Kulnane, L.S.; Nixon, R.A.; Lamb, B.T.; Epstein, C.J.; Stokin, G.B.; Goldstein, L.S.; Mobley, W.C. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron, 2006, 51(1), 29 42.
134. Williams, L.R. Hypophagia is induced by intracerebroventricular administration of nerve growth factor. Exp. Neurol., 1991, 113(1), 31-37.
135. Isaacson, L.G.; Saffran, B.N.; Crutcher, K.A. Intracerebral NGF infusion induces hyperinnervation of cerebral blood vessels. Neurobiol. Aging, 1990, 11(1), 51-55.
136. Emmett, C.J.; Stewart, G.R.; Johnson, R.M.; Aswani, S.P.; Chan, R.L.; Jakeman, L.B. Distribution of radioiodinated recombinant human nerve growth factor in primate brain following intracerebroventricular infusion. Exp. Neurol., 1996, 140(2), 151-160.
137. Winkler, J.; Ramirez, G.A.; Kuhn, H.G.; Peterson, D.A.; Day Lollini, P.A.; Stewart, G.R.; Tuszynski, M.H.; Gage, F.H.; Thal, L.J. Reversible Schwann cell hyperplasia and sprouting of sensory and sympathetic neurites after intraventricular administration of nerve growth factor. Ann. Neurol., 1997, 41(1), 82-93.
138. Eriksdotter Jonhagen, M.; Nordberg, A.; Amberla, K.; Backman, L.; Ebendal, T.; Meyerson, B.; Olson, L.; Seiger; Shigeta, M.; Theodorsson, E.; Viitanen, M.; Winblad, B.; Wahlund, L.O. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord., 1998, 9(5), 246-257.
139. Kordower, J.H.; Palfi, S.; Chen, E.Y.; Ma, S.Y.; Sendera, T.; Cochran, E.J.; Mufson, E.J.; Penn, R.; Goetz, C.G.; Comella, C.D. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann. Neurol., 1999, 46(3), 419-424.
140. Nutt, J.G.; Burchiel, K.J.; Comella, C.L.; Jankovic, J.; Lang, A.E.; Laws, E.R., Jr.; Lozano, A.M.; Penn, R.D.; Simpson, R.K., Jr.; Stacy, M.; Wooten, G.F. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology, 2003, 60(1), 69-73.
141. Cleveland, D.W.; Rothstein, J.D. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci., 2001, 2(11), 806-819.
142. Julien, J.P. Amyotrophic lateral sclerosis. unfolding the toxicity of the misfolded. Cell, 2001, 104(4), 581-591.
143. Doble, A. The pharmacology and mechanism of action of riluzole. Neurology, 1996, 47(6 Suppl 4), S233-241.
144. Peluffo, H.; Estevez, A.; Barbeito, L.; Stutzmann, J.M. Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic activity produced by spinal astrocyte monolayers. Neurosci. Lett., 1997, 228(3), 207-211.
145. Brown, R.H., Jr. Amyotrophic lateral sclerosis: recent insights from genetics and transgenic mice. Cell., 1995, 80(5), 687-692.
146. Andersen, P.M.; Sims, K.B.; Xin, W.W.; Kiely, R.; O'Neill, G.; Ravits, J.; Pioro, E.; Harati, Y.; Brower, R.D.; Levine, J.S.; Heinicke, H.U.; Seltzer, W.; Boss, M.; Brown, R.H., Jr. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph. Latera. Scler. Other Motor Neuron Disord., 2003, 4(2), 62-73.
147. Garbuzova-Davis, S.; Willing, A.E.; Milliken, M.; Saporta, S.; Zigova, T.; Cahill, D.W.; Sanberg, P.R. Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis. Exp. Neurol., 2002, 174(2), 169-180.
148. Corti, S.; Locatelli, F.; Donadoni, C.; Guglieri, M.; Papadimitriou, D.; Strazzer, S.; Del Bo, R.; Comi, G.P. Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and contribute to CNS, heart and skeletal muscle tissues. Brain., 2004, 127(Pt 11), 2518-2532.
149. Hemendinger, R.; Wang, J.; Malik, S.; Persinski, R.; Copeland, J.; Emerich, D.; Gores, P.; Halberstadt, C.; Rosenfeld, J. Sertoli cells improve survival of motor neurons in SOD1 transgenic mice, a model of amyotrophic lateral sclerosis. Exp. Neurol., 2005, 196(2), 235-243.
150. Yan, J.; Xu, L.; Welsh, A.M.; Chen, D.; Hazel, T.; Johe, K.; Koliatsos, V.E. Combined immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice. Stem Cells, 2006, 24(8), 1976-1985.
151. Habisch, H.J.; Janowski, M.; Binder, D.; Kuzma-Kozakiewicz, M.; Widmann, A.; Habich, A.; Schwalenstocker, B.; Hermann, A.; Brenner, R.; Lukomska, B.; Domanska-Janik, K.; Ludolph, A.C.; Storch, A. Intrathecal application of neuroectodermally converted stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects. J. Neural. Transm., 2007, 114(11), 1395-1406.
152. Garbuzova-Davis, S.; Klasko, S.K.; Sanberg, P.R. Intravenous administration of human umbilical cord blood cells in an animal model of MPS III B. J. Comp. Neurol., 2009, 515(1), 93-101.
153. Svendsen, C.N.; ter Borg, M.G.; Armstrong, R.J.; Rosser, A.E.; Chandran, S.; Ostenfeld, T.; Caldwell, M.A. A new method for the rapid and long term growth of human neural precursor cells. J. Neurosci. Methods, 1998, 85(2), 141-152.
154. Teng Y.D.; Benn S.C.; Kalkanis S.N.; Shefner J.M.; Onario R.C.; Cheng B.; Lachyankar M.B.; Macconi M.; Li J.; Maragakis N.J.; Lládo J.; Erkmen K.; Redmond D.E. Jr.; Sidman R.L.; Przedborski S.; Rothstein J.D.; Brown R.H. Jr.; Snyder E.Y. Neural stem cells, acting through multiple mechanisms, extensively prolong life and preserve function in a mouse model of ALS. 2010 to be submitted.
155. Xu, L.; Yan, J.; Chen, D.; Welsh, A.M.; Hazel, T.; Johe, K.; Hatfield, G.; Koliatsos, V.E. Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation, 2006, 82(7), 865-875.
156. Klein, S.M.; Behrstock, S.; McHugh, J.; Hoffmann, K.; Wallace, K.; Suzuki, M.; Aebischer, P.; Svendsen, C.N. GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum. Gene Ther., 2005, 16(4), 509-521.
157. Guillot, S.; Azzouz, M.; Deglon, N.; Zurn, A.; Aebischer, P. Local GDNF expression mediated by lentiviral vector protects facial nerve motoneurons but not spinal motoneurons in SOD1(G93A) transgenic mice. Neurobiol. Dis., 2004, 16(1), 139-149.
158. Suzuki, M.; McHugh, J.; Tork, C.; Shelley, B.; Klein, S.M.; Aebischer, P.; Svendsen, C.N. GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS One, 2007, 2(1), e689.
159. Mazzini, L.; Ferrero, I.; Luparello, V.; Rustichelli, D.; Gunetti, M.; Mareschi, K.; Testa, L.; Stecco, A.; Tarletti, R.; Miglioretti, M.; Fava, E.; Nasuelli, N.; Cisari, C.; Massara, M.; Vercelli, R.; Oggioni, G.D.; Carriero, A.; Cantello, R.; Monaco, F.; Fagioli, F. Mesenchymal stem Cell Transplant. ation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp. Neurol., 2010, 223(1), 229-237.
160. Group A-CTS. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology, 1996, 46(5), 1244-1249.
161. Group TBS. A controlled trial of recombinant methionyl human BDNF in ALS: The BDNF Study Group (Phase III). Neurology, 1999, 52(7), 1427-1433.
162. Nagai, M.; Re, D.B.; Nagata, T.; Chalazonitis, A.; Jessell, T.M.; Wichterle, H.; Przedborski, S. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat. Neurosci., 2007, 10(5), 615-622.
163. Yamanaka, K.; Chun, S.J.; Boillee, S.; Fujimori-Tonou, N.; Yamashita, H.; Gutmann, D.H.; Takahashi, R.; Misawa, H.; Cleveland, D.W. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci., 2008, 11(3), 251-253.
164. Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126(4), 663-676.
165. Pick, M.; Stelzer, Y.; Bar-Nur, O.; Mayshar, Y.; Eden, A.; Benvenisty, N. Clone and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells, 2009, 27(11), 2686-2690.
166. Marchetto, M.C.; Yeo, G.W.; Kainohana, O.; Marsala, M.; Gage, F.H.; Muotri, A.R. Transcriptional sigNature. and memory retention of human-induced pluripotent stem cells. PLoS One, 2009, 4(9), e7076.
167. Ghosh, Z.; Wilson, K.D.; Wu, Y.; Hu, S.; Quertermous, T.; Wu, J.C. Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells. PLoS One, 2010, 5(2), e8975.
168. Heng, J.C.; Feng, B.; Han, J.; Jiang, J.; Kraus, P.; Ng, J.H.; Orlov, Y.L.; Huss, M.; Yang, L.; Lufkin, T.; Lim, B.; Ng, H.H. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell, 2010, 6(2), 167-174.
169. O'Malley, J.; Woltjen, K.; Kaji, K. New strategies to generate induced pluripotent stem cells. Curr. Opin. Biotechnol., 2009, 20(5), 516-521.
170. Huangfu, D.; Osafune, K.; Maehr, R.; Guo, W.; Eijkelenboom, A.; Chen, S.; Muhlestein, W.; Melton, D.A. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol., 2008, 26(11), 1269-1275.
171. Kim, J.B.; Greber, B.; Arauzo-Bravo, M.J.; Meyer, J.; Park, K.I.; Zaehres, H.; Scholer, H.R. Direct reprogramming of human neural stem cells by OCT4. Nature, 2009, 461(7264), 649-643.
172. Kim, J.B.; Sebastiano, V.; Wu, G.; Arauzo-Bravo, M.J.; Sasse, P.; Gentile, L.; Ko, K.; Ruau, D.; Ehrich, M.; van den Boom, D.; Meyer, J.; Hubner, K.; Bernemann, C.; Ortmeier, C.; Zenke, M.; Fleischmann, B.K.; Zaehres, H.; Scholer, H.R. Oct4-induced pluripotency in adult neural stem cells. Cell, 2009, 136(3), 411-419.
173. Kim, J.B.; Zaehres, H.; Wu, G.; Gentile, L.; Ko, K.; Sebastiano, V.; Arauzo-Bravo, M.J.; Ruau, D.; Han, D.W.; Zenke, M.; Scholer, H.R. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 2008, 454(7204), 646-650.
174. Stadtfeld, M.; Nagaya, M.; Utikal, J.; Weir, G.; Hochedlinger, K. Induced pluripotent stem cells generated without viral integration. Science, 2008, 322(5903), 945-949.
175. Lyssiotis, C.A.; Foreman, R.K.; Staerk, J.; Garcia, M.; Mathur, D.; Markoulaki, S.; Hanna, J.; Lairson, L.L.; Charette, B.D.; Bouchez, L.C.; Bollong, M.; Kunick, C.; Brinker, A.; Cho, C.Y.; Schultz, P.G.; Jaenisch, R. Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc. Natl. Acad. Sci. USA, 2009, 106(22), 8912-8917.
176. Gonzalez, F.; Barragan Monasterio, M.; Tiscornia, G.; Montserrat Pulido, N.; Vassena, R.; Batlle Morera, L.; Rodriguez Piza, I.; Izpisua Belmonte, J.C. Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector. Proc. Natl. Acad. Sci. USA, 2009, 106(22), 8918-8922.
177. Yu, J.; Hu, K.; Smuga-Otto, K.; Tian, S.; Stewart, R.; Slukvin, II; Thomson, J.A. Human induced pluripotent stem cells free of vector and transgene sequences. Science, 2009, 324(5928), 797-801.
178. Okita, K.; Hong, H.; Takahashi, K.; Yamanaka, S. Generation of mouse-induced pluripotent stem cells with plasmid vectors. Nat. Protoc., 2010, 5(3), 418-428.
179. Dimos, J.T.; Rodolfa, K.T.; Niakan, K.K.; Weisenthal, L.M.; Mitsumoto, H.; Chung, W.; Croft, G.F.; Saphier, G.; Leibel, R.; Goland, R.; Wichterle, H.; Henderson, C.E.; Eggan, K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 2008, 321(5893), 1218 1221.
180. Maehr, R.; Chen, S.; Snitow, M.; Ludwig, T.; Yagasaki, L.; Goland, R.; Leibel, R.L.; Melton, D.A. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc. Natl. Acad. Sci. USA, 2009, 106(37), 15768-15773.
181. Miyoshi, N.; Ishii, H.; Nagai, K.; Hoshino, H.; Mimori, K.; Tanaka, F.; Nagano, H.; Sekimoto, M.; Doki, Y.; Mori, M. Defined factors induce reprogramming of gastrointestinal cancer cells. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 40-45.
182. Zhou, Q.; Brown, J.; Kanarek, A.; Rajagopal, J.; Melton, D.A. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature, 2008, 455(7213), 627-632.
183. Warren, L.; Manos, P.D.; Ahfeldt, T.; Loh, Y.H.; Li, H.; Lau, F.; Ebina, W.; Mandal, P.K.; Smith, Z.D.; Meissner, A.; Daley, G.Q.; Brack, A.S.; Collins, J.J.; Cowan, C.; Schlaeger, T.M.; Rossi, D.c. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 2010, Sep 29. [Epub ahead of print]
184. Kim, K.; Doi, A.; Wen, B.; Ng, K.; Zhao, R.; Cahan, P.; Kim, J.; Aryee, M.J.; Ji, H.; Ehrlich, L.I.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K.C.; Hongguang, H.; McKinney-Freeman, S.; Naveiras, O.; Yoon, T.J.; Irizarry, R.A.; Jung, N.; Seita, J.; Hanna, J.; Murakami, P.; Jaenisch, R.; Weissleder, R.; Orkin, S.H.; Weissman, I.L.; Feinberg, A.P.; Daley, G.Q. Epigenetic memory in induced pluripotent stem cells. Nature, 2010, 467(7313), 285-290.
185. Polo, J.M.; Liu, S.; Figueroa, M.E.; Kulalert, W.; Eminli, S.; Tan, K.Y.; Apostolou, E.; Stadtfeld, M.; Li, Y.; Shioda, T.; Natesan, S.; Wagers, A.J.; Melnick, A.; Evans, T.; Hochedlinger, K. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat. Biotechnol., 2010, 28(8), 848-855.
186. Ji, H.; Ehrlich, L.I.; Seita, J.; Murakami, P.; Doi, A.; Lindau, P.; Lee, H.; Aryee, M.J.; Irizarry, R.A.; Kim, K.; Rossi, D.J.; Inlay, M.A.; Serwold, T.; Karsunky, H.; Ho, L.; Daley, G.Q.; Weissman, I.L.; Feinberg, A.P. Comprehensive methylome map of lineage commitment from haematopoietic progenitors. Nature, 2010, 467(7313), 338-342.