Stem Cells: Cellular and Drug Therapies. Volume 2

Philippe Taupin, PhD
Dublin City University, School of Biotechnology, Dublin, Ireland

Series: Stem Cells – Laboratory and Clinical Research
BISAC: SCI017000

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Special issue: Resilience in breaking the cycle of children’s environmental health disparities
Edited by I Leslie Rubin, Robert J Geller, Abby Mutic, Benjamin A Gitterman, Nathan Mutic, Wayne Garfinkel, Claire D Coles, Kurt Martinuzzi, and Joav Merrick

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Stem cells are the building blocks of the body. They can develop into any of the cells that make up our bodies. Stem cells carry a lot of hope for the treatment of a broad range of diseases and injuries, spanning from cancers, diabetes, genetic diseases, graft-versus-host disease, eye, heart and liver diseases, inflammatory and autoimmune disorders, to neurological diseases and injuries, particularly neurodegenerative diseases, like Alzheimer’s and Parkinson’s diseases, cerebral strokes, and traumatic brain and spinal cord injuries. Stem cell research is therefore as important for our understanding the physio- and pathology of the body, as for development and therapy, including for the nervous system.

This book aims at providing an overview and in depth analysis of recent developments in stem cell research and therapy. It is composed of recently published review articles that went through a peer-review process. (Imprint: Nova Biomedical )

Introduction

Chapter 1. Adult Neurogenesis in Etiology and Pathogenesis of Alzheimer’s Disease

Chapter 2. Adult Neurogenesis and Aneuploidy in Etiology, Pathogenesis and Pathology of Alzheimer’s Disease

Chapter 3. Adult Neurogenesis, Neural Stem Cells and Alzheimer’s Disease: Developments, Limitations, Problems and Promises

Chapter 4. Oxidative Stress in Adult Neurogenesis and in the Pathogenesis of Alzheimer's Disease

Chapter 5. Adult Neurogenesis, Neuroinflamation, and Therapeutic Potential of Adult Neural Stem Cells

Chapter 6. Adult Neurogenesis and Drug Therapy

Chapter 7. Neurogenesis and the Effect of Antidepressants

Chapter 8. Neurogenic Drugs and Compounds to Treat CNS Diseases and Disorders

Chapter 9. Patent Evaluation. Thirteen Compounds Promoting Oligodendrocyte Progenitor Cell Differentiation and Remyelination for Treating Multiple Sclerosis: Wo2010054307

Chapter 10. Patent Evaluation. Antibodies against CD20 (Rituximab) for Treating Multiple Sclerosis: US20100233121

Chapter 11. Umbilical Cord Blood and Alpha-3 Fucosyl Transferase-Treated Haematopoietic Stem Cells for Transplantation

Chapter 12. Patent Evaluation. Cell Lines Expressing Mutant FX Proteins to Generate Proteins with Reduced Rate of Fucosylation: Wo2010/141478

Chapter 13. Patent Evaluation. Modulation of GDP-Fucose Level for Generating Proteins with Reduced Rate of Fucosylation (Wo2010141855)

Chapter 14. Patent Evaluation. Chimeric Proteins Comprising the Constant Region of Immunoglobulins for Treating Haemophilia B (WO2005001025)

Chapter 15. Patent Evaluation Parthenogenetically Activated Human Oocytes and Parthenogenetic Embryonic Stem Cells: US20100233143

Chapter 16. Tuberous Sclerosis Complex: A Paradigm for Studying Adult Neurogenesis and Brain Tumors

Chapter 17. Adult Neurogenesis in Alzheimer’s Disease and Therapies

Chapter 18. Indacaterol for the Treatment of Patients with Moderate-to-Severe COPD

Conclusions

Index

Introduction

[1] Taupin, P. (2006) Neurogenesis in the adult central nervous system. C. R. Biol. 329, 465-475.
[2] Jin, K. et al. (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc. Natl. Acad. Sci. U. S. A. 101, 343-347.
[3] Querfurth, H.W. et al. (2010) Alzheimer’s disease. N. Engl. J. Med. 362, 329-344.
[4] Kingsbury, M.A. et al. (2006) Aneuploidy in the normal and diseased brain. Cell. Mol. Life. Sci. 63, 2626-2641.
[5] Yang, Y. et al. (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J. Neurosci. 23, 2557-2563.
[6] Yang, Y. et al. (2007) Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim. Biophys. Acta 1772, 457-466.
[7] Torres, E.M. et al. (2008) Aneuploidy: cells losing their balance. Genetics 179, 737-746.
[8] Taupin, P. (2009) Adult neurogenesis, neural stem cells and Alzheimer’s disease: developments, limitations, problems and promises. Curr. Alzheimer Res. 6, 461-470.
[9] Li, J. et al. (1997) Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90, 917-927.
[10] Kim, H. et al. (1986) The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure. Ann. N. Y. Acad. Sci. 466, 218-239.

Chapter 1

Anderson DH, Talaga KC, Rivest AJ, Barron E, Hageman GS, Johnson LV (2004) Characterization of beta amyloid assemblies in drusen: The deposits associated with aging and age-related macular degeneration. Exp. Eye Res. 78:243–256.
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Boeras DI, Granic A, Padmanabhan J, Crespo NC, Rojiani AM, Potter H (2008) Alzheimer’s presenilin 1 causes chromosome missegregation and aneuploidy. Neurobiol. Aging 29:319–328.
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Brundin P, Barker RA, Parmar M (2010) Neural grafting in Parkinson’s disease: Problems and possibilities. Progr. Brain Res. 184:265–294.
Burns A, Byrne EJ, Maurer K (2002) Alzheimer’s disease. Lancet 13:163–165.
Busser J, Geldmacher DS, Herrup K (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer’s disease brain. J. Neurosci. 18:2801–2807.
Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344.
Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RL, Eriksson PS (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315: 1243–1249.
Duan X, Kang E, Liu CY, Ming GL, Song H (2008) Development of neural stem cell in the adult brain. Curr. Opin. Neurobiol. 18:108–115.
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O’brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P (2007) Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS -ADRDA criteria. Lancet Neurol. 6:734–746.
Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat. Med. 4:1313–1317.
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M, Alzheimer’s Disease International (2005) Global prevalence of dementia: A Delphi consensus study. Lancet 366:2112–2117.
Filipcik P, Cente M, Ferencik M, Hulin I, Novak M (2006) The role of oxidative stress in the pathogenesis of Alzheimer’s disease. Bratisl Lek. Listy 107:384–394.
Fukutani Y, Kobayashi K, Nakamura I, Watanabe K, Isaki K, Cairns NJ (1995) Neurons, intracellular and extra cellular neurofibrillary tangles in subdivisions of the hippocampal cortex in normal ageing and Alzheimer’s disease. Neurosci. Lett 200:57–60.
Fusetti M, Fioretti AB, Silvagni F, Simaskou M, Sucapane P, Necozione S, Eibenstein A (2010) Smell and preclinical Alzheimer disease: Study of 29 patients with amnesic mild cognitive impairment. J. Otolaryngol. Head Neck Surg. 39:175–181.
Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438.
Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease. Science 235:877–880.
Gould E, Gross GC (2002) Neurogenesis in adult mammals: some progress and problems. J. Neurosci. 22:619–623.
Herrup K, Arendt T (2002) Re-expression of cell cycle proteins induces neuronal cell death during Alzheimer’s disease. J. Alzheimer’s Dis. 4:243–247.
Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 118:53–69.
Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004a) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 101: 343–347.
Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA (2004b) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw,Ind) mice. Proc. Natl. Acad. Sci. USA 101:13363–13367.
Kaneko Y, Sakakibara S, Imai T, Suzuki A, Nakamura Y, Sawamoto K, Ogawa Y, Toyama Y, Miyata T, Okano H (2000) Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev. Neurosci. 22:139–153.
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733–736.
Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495.
Kim H, Jensen CG, Rebhun LI (1986) The binding of MAP-2 and tau on brain microtubules in vitro: Implications for microtubule structure. Ann. N. Y. Acad. Sci. 466:218–239.
Kingsbury MA, Yung YC, Peterson SE, Westra JW, Chun J (2006) Aneuploidy in the normal and diseased brain. Cell. Mol. Life Sci. 63:2626–2641.
Komitova M, Eriksson PS (2004) Sox-2 is expressed by neural progenitors and astroglia in the adult rat brain. Neurosci. Lett. 369:24–27.
Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595.
Li J, Xu M, Zhou H, Ma J, Potter H (1997) Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90:917–927.
LiW, Howard JD, Gottfried JA (2010) Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer’s disease. Brain 133:2714–2726.
Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148.
Migliore L, Botto N, Scarpato R, Petrozzi L, Cipriani G, Bonuccelli U (1999) Preferential occurrence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients. Cytogenet. Cell Genet. 87:41–46.
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Nishimura M, Yu G, St George-Hyslop PH (1999) Biology of presenilins as causative molecules for Alzheimer disease. Clin. Genet. 55:219–225.
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Palmer TD, Schwartz PH, Taupin P, Kaspar B, Stein SA, Gage FH (2001) Cell culture. Progenitor cells from human brain after death. Nature 411:42–43.
Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422:688–694.
Prasher VP, Haque MS (2000) Apolipoprotein E, Alzheimer’s disease and Down’s syndrome. Br. J. Psychiatry 177:469–470.
Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N. Engl. J. Med. 362:329–344.
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710.
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St George-Hyslop PH, Petit A (2005) Molecular biology and genetics of Alzheimer’s disease. C. R. Biol. 328:119–130.
Taupin P (2007a) Protocols for studying adult neurogenesis: Insights and recent developments. Regener. Med. 2:51–62.
Taupin P (2007b) BrdU immunohistochemistry for studying adult neurogenesis: Paradigms, pitfalls, limitations, and validation. Brain Res. Rev. 53:198–214.
Taupin P (2009a) Characterization and isolation of synapses of newly generated neuronal cells of the adult hippocampus at early stages of neurogenesis. J. Neurodegener Regener. 2: 9–17.
Taupin P (2009b) Adult neurogenesis, neural stem cells and Alzheimer’s disease: Developments, limitations, problems and promises. Curr. Alzheimer Res. 6:461–470.
Taupin P (2010a) Ex vivo fucosylation to improve the engraftment capability and therapeutic potential of human cord blood stem cells. Drug Discov. Today 15:698–699.
Taupin P (2010b) Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 7:703–715.
Taupin P (2010c) Adult neurogenesis and neural stem cells as a model for the discovery and development of novel drugs. Expert Opin. Drug Discov. 5:921–925.
Taupin P (2010d) A dual activity of ROS and oxidative stress on adult neurogenesis and Alzheimer’s disease. Central Nervous Syst. Agents Med. Chem. 10:16–21.
Taupin P, Gage FH (2002) Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neurosci. Res. 69:745–749.
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Yang Y, Herrup K (2007) Cell division in the CNS: Protective response or lethal event in post-mitotic neurons? Biochim. Biophys. Acta 1772:457–466.
Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer’s disease. J. Neurosci. 21:2661–2668.
Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J. Neurosci. 23:2557–2563.
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Ziabreva I, Perry E, Perry R, Minger SL, Ekonomou A, Przyborski S, Ballard C (2006) Altered neurogenesis in Alzheimer’s disease. J. Psychosom. Res. 61:311–316.

Chapter 2

[1] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y., Jorm, A., Mathers, C., Menezes, P.R., Rimmer, E. and Scazufca, M.; Alzheimer's Disease International. (2005) Global prevalence of dementia: a Delphi consensus study. Lancet, 366, 2112-7.
[2] Burns, A., Byrne, E.J. and Maurer, K. (2002) Alzheimer’s disease. Lancet, 360, 163-5.
[3] Querfurth, H.W. and LaFerla F.M. (2010) Alzheimer's disease. N. Engl. J. Med., 362, 329-44.
[4] Anderson, D.H., Talaga, K.C., Rivest, A.J., Barron, E., Hageman, G.S. and Johnson, L.V. (2004) Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp. Eye Res., 78, 243-56.
[5] Kang, J., Lemaire, H.G., Unterbeck, A., Salbaum, J.M., Masters, C.L., Grzeschik. K.H., Multhaup. G., Beyreuther. K. and Müller-Hill, B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325, 733-6.
[6] Nishimura, M., Yu, G. and St George-Hyslop, P.H. (1999) Biology of presenilins as causative molecules for Alzheimer disease. Clin. Genet., 55, 219-25.
[7] Wang, J.F., Lu, R., and Wang, Y.Z. (2010) Regulation of β cleavage of amyloid precursor protein. Neurosci. Bull., 26, 417-27.
[8] Fukutani, Y., Kobayashi, K., Nakamura, I., Watanabe, K., Isaki, K. and Cairns, N.J. (1995) Neurons, intracellular and extra cellular neurofibrillary tangles in subdivisions of the hippocampal cortex in normal ageing and Alzheimer's disease. Neurosci. Lett., 200, 57-60.
[9] Kim, H., Jensen, C.G. and Rebhun, L.I. (1986) The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure. Ann. N. Y. Acad. Sci., 466, 218-39.
[10] Iqbal, K., Liu, F., Gong, C.X., Alonso Adel, C. and Grundke-Iqbal, I. (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol., 118, 53-69.
[11] Nishimura, M., Yu, G. and St George-Hyslop, P.H. (1999) Biology of presenilins as causative molecules for Alzheimer disease. Clin. Genet., 55, 219-225.
[12] St George-Hyslop, P.H. and Petit, A. (2005) Molecular biology and genetics of Alzheimer's disease. C. R. Biol., 328, 119-30.
[13] Wang, X. P. and Ding, H. L. (2008) Alzheimer's disease: epidemiology, genetics, and beyond. Neurosci. Bull., 24, 105-9.
[14] Prasher, V.P. and Haque, M.S. (2000) Apolipoprotein E, Alzheimer's disease and Down's syndrome. Br. J. Psychiatry, 177, 469-70.
[15] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Filipcik, P., Cente, M., Ferencik, M., Hulin, I. and Novak, M. (2006) The role of oxidative stress in the pathogenesis of Alzheimer's disease. Bratisl Lek Listy, 107, 384-94.
[16] Brun, A. and Gustafson, L. (1976) Distribution of cerebral degeneration in Alzheimer's disease. A clinico-pathological study. Arch. Psychiatr. Nervenkr., 223, 15-33.
[17] Christen-Zaech, S., Kraftsik, R., Pillevuit, O., Kiraly, M., Martins, R., Khalili, K. and Miklossy, J. (2003) Early olfactory involvement in Alzheimer's disease. Can. J. Neurol. Sci, 30, 20-5.
[18] Fusetti, M., Fioretti, AB., Silvagni, F., Simaskou, M., Sucapane, P., Necozione, S. and Eibenstein, A. (2010) Smell and preclinical Alzheimer disease: study of 29 patients with amnesic mild cognitive impairment. J. Otolaryngol. Head Neck Surg., 39, 175-81.
[19] Migliore, L., Testa, A., Scarpato, R., Pavese, N., Petrozzi, L. and Bonuccelli, U. (1997) Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease. Hum. Genet., 101, 299-305.
[20] Busser, J., Geldmacher, D.S. and Herrup, K. (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J. Neurosci., 18, 2801-7.
[21] Kingsbury, M.A., Yung, Y.C., Peterson, S.E., Westra, J.W. and Chun, J. (2006) Aneuploidy in the normal and diseased brain. Cell. Mol. Life Sci., 63, 2626-41.
[22] Yang, Y., Mufson, E.J. and Herrup, K. (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J. Neurosci., 23, 2557-63.
[23] Yang, Y. and Herrup, K. (2007) Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim. Biophys. Acta, 1772, 457-66.
[24] Goldgaber, D., Lerman, M.I., McBride, O.W., Saffiotti, U. and Gajdusek, D.C. (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science, 235, 877-80.
[25] Taupin, P. (2009) Adult neurogenesis, neural stem cells and Alzheimer’s disease: developments, limitations, problems and promises. Curr. Alzheimer. Res., 6, 461-70.
[26] Taupin, P. and Gage, F.H. (2002) Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neur. Res., 69, 745-9.
[27] Duan, X., Kang, E., Liu, C.Y., Ming, G.L. and Song, H. (2008) Development of neural stem cell in the adult brain. Curr. Opin. Neurobiol., 18, 108-15.
[28] Toni, N., Teng, EM.., Bushong, E.A., Aimone, J.B., Zhao, C., Consiglio, A., van Praag, H., Martone, M.E., Ellisman, M.H. and Gage, F.H. (2007) Synapse formation on neurons born in the adult hippocampus. Nat. Neurosci., 10, 727-34.
[29] Taupin, P. (2009) Characterization and isolation of synapses of newly generated neuronal cells of the adult hippocampus at early stages of neurogenesis. J. Neurodeg. Regen., 2, 9-17.
[30] Reynolds, B.A. and Weiss, S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 255, 1707-10.
[31] Palmer, T.D., Schwartz, P.H. Taupin, P., Kaspar, B., Stein, S.A. and Gage, F.H. (2001) Cell culture. Progenitor cells from human brain after death. Nature, 411, 42-3.
[32] Pluchino, S., Quattrini, A., Brambilla, E., Gritti, A., Salani, G., Dina, G., Galli, R., Del Carro, U., Amadio, S., Bergami, A., Furlan, R., Comi, G., Vescovi, A.L. and Martino, G. (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature, 422, 688-94.
[33] Taupin, P. (2010) Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy, 7, 703-15.
[34] Jin, K., Peel, A.L., Mao, X.O., Xie, L., Cottrell, B.A., Henshall, D.C. and Greenberg, D.A. (2004) Increased hippocampal neurogenesis in Alzheimer's disease. Proc. Natl. Acad. Sci. U S A, 101, 343-7.
[35] Ziabreva, I., Perry, E., Perry, R., Minger, S.L., Ekonomou, A., Przyborski, S. and Ballard, C. (2006) Altered neurogenesis in Alzheimer's disease. J. Psychosom. Res., 61, 311-6.
[36] Li, W., Howard, J.D., and Gottfried, J.A. (2010) Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer's disease. Brain, 133, 2714-26.
[37] Gould, E. and Gross, C.G. (2002) Neurogenesis in adult mammals: some progress and problems. J. Neurosci., 22, 619-23.
[38] Taupin, P. (2007) Protocols for Studying Adult Neurogenesis: Insights and Recent Developments. Regen. Med., 2, 51-62.
[39] Taupin, P. (2010) A dual activity of ROS and oxidative stress on adult neurogenesis and Alzheimer’s disease. Cent. Nerv. Syst. Agents Med. Chem., 10, 16-21.

Chapter 3

[1] Alzheimer A. Uber einen eigenartigen schweren erkrankungsprozeb der hirnrinde. Neurologisches cenrealblatt 23: 1129-1136 (1906).
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[4] Burns A, Byrne EJ and Maurer K. Alzheimer’s disease. Lancet 360: 163-165 (2002).
[5] Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet 366: 2112-2117 (2005).
[6] Gross CG. Neurogenesis in the adult brain: death of a dogma. Nat. Rev. Neurosci. 1: 67-73 (2000).
[7] Taupin P. Neurogenesis in the adult central nervous system. C. R. Biol. 329: 465-475 (2006).
[8] Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA et al. Neurogenesis in the adult human hippocampus. Nat. Med. 4: 1313-1317 (1998).
[9] Bedard A and Parent A. Evidence of newly generated neurons in the human olfactory bulb. Brain Res. Dev. Brain Res. 151: 159-168 (2004).
[10] Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315: 1243-1249 (2007).
[11] Taupin P and Gage FH. Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neurosci. Res. 69: 745-749 (2002).
[12] Gage FH. Mammalian neural stem cells. Science 287: 1433-1438 (2000).
[13] Parent JM, Tada E, Fike JR, Lowenstein DH. Inhibition of dentate granule cell neurogenesis with brain irradiation does not prevent seizure-induced mossy fiber synaptic reorganization in the rat. J. Neurosci. 19: 4508-4519 (1999).
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Chapter 4

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Taupin P (2010c) Ex vivo fucosylation to improve the engraftment capability and therapeutic potential of human cord blood stem cells. Drug Discovery Today 15:698–699.
Taupin P (2011) Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US 20100233121. Exp Opin Ther Patents 21:111-114.
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Chapter 12

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[3] Upreti RK, Kumar M, Shankar V. Bacterial glycoproteins: functions, biosynthesis and applications. Proteomics 2003;3:363-79.
[4] Taupin P, Ray J, Fischer WH, et al. FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 2000;28:385-97.
** The glycosylation of CCg is required for its activity as a neural stem cell factor, co-factor of FGF-2.
[5] Taupin P. Ex vivo fucosylation to improve the engraftment capability and therapeutic potential of human cord blood stem cells. Drug Discovery Today 2010;15:698-9.
[6] Taupin P. Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 2010;7:703-15.

** Treatment of cord blood tissue with FTVI, prior transplantation, improves the homing and engraftment of cord blood stem cells to the bone marrow.
[7] Moriwaki K, Miyoshi E. Fucosylation and gastrointestinal cancer. World J Hepatol 2010;2:151-61.
[8] Miyoshi E, Moriwaki K, Nakagawa T. Biological function of fucosylation in cancer biology. J Biochem 2008;143:725-9.
[9] Weninger W, Ulfman LH, Cheng G, et al. Specializedcontributions by a(1,3)-fucosyltransferase-IV and FucT-VII during leukocyte rolling in dermal microvessels. Immunity 2000;12:665-76.
[10] Taupin P. Ex vivo fucosylation of stem cells to improve engraftment: WO2004094619. Expert Opinion on Therapeutic Patents 2010;20:1265-9.
[11] Becker DJ, Lowe JB. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003;13:41R-53R.
** The FX gene is highly conserved in mammals.
[12] Huhn C, Selman MH, Ruhaak LR, et al. IgG glycosylation analysis. Proteomics. 2009;9:882-913.
[13] Taupin P. Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US 20100233121. Expert Opinion on Therapeutic Patents. 2011; 21(1):111-114.
[14] Masuda A, Yoshida M, Shiomi H, et al. Role of Fc Receptors as a therapeutic target. Inflamm Allergy Drug Targets 2009;8:80-6.
[15] Taupin P. Hybrid proteins comprising the constant region of immunoglobulins for treating haemophilia B. Expert Opinion on Therapeutic Patents. 2011; In press.
[16] Jefferis R. Antibody therapeutics: isotype and glycoform selection. Expert Opin Biol Ther. 2007;7:1401-13.

** Antibodies that lack fucosylation can mediate antibody-dependent cell-mediated cytotoxicity better than fucosylated antibodies.
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[19] Malphettes L, Freyvert Y, Chang J, et al. Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol Bioeng 2010;106:774-83.

Chapter 13

[1] Taupin P, Ray J, Fischer WH, et al. FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 2000;28:385-97.

•• The glycosylation of CCg is required for its activity as a neural stem cell factor, co-factor of FGF-2.
[2] Taupin P. Ex vivo fucosylation to improve the engraftment capability and therapeutic potential of human cord blood stem cells. Drug Discovery Today 2010;15:698-9.
[3] Moriwaki K, Miyoshi E. Fucosylation and gastrointestinal cancer. World J Hepatol 2010;2:151-61.
[4] Taupin P. Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 2010;7:703-15.

•• Treatment of cord blood tissue with FTVI, prior transplantation, improves the homing and engraftment of cord blood stem cells to the bone marrow.
[5] Moens S, Vanderleyden J. Glycoproteins in prokaryotes. Arch Microbiol 1997;168:169-75.
[6]

••Prokaryotes (Archaea and Bacteria) are able to synthesize glycoproteins.
Hudson JE, Johnson TC. The degradation and turnover of fucosylated glycoproteins in the plasma membrane of a neuroblastoma-cell line. Biochem J 1977;166:217-23.
[7] Jefferis R. Antibody therapeutics: isotype and glycoform selection. Expert Opin Biol Ther. 2007;7:1401-13.
[8] Taupin P. Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US 20100233121. Expert Opinion on Therapeutic Patents. 2011; 21(1):111-114.
[9] Taupin P. Hybrid proteins comprising the constant region of immunoglobulins for treating haemophilia B. Expert Opinion on Therapeutic Patents. 2011; In press.
[10] Miyoshi E, Moriwaki K, Nakagawa T. Biological function of fucosylation in cancer biology. J Biochem 2008;143:725-9.
[11] Taupin P. Ex vivo fucosylation of stem cells to improve engraftment: WO2004094619. Expert Opinion on Therapeutic Patents 2010;20:1265-9.
[12] Bengtson P, Lundblad A, Larson G, et al. Polymorphonuclear leukocytes from individuals carrying the G329A mutation in the 1,3-fucosyltransferase VII gene (FUT7) roll on E- and P-selectins. J Immunol 2002;169:3940-6.
[13] Becker DJ, Lowe JB. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003;13:41R-53R.
[14] Reitman ML, Trowbridge IS, Kornfeld S. Mouse lymphoma cell lines resistant to pea lectin are defective in fucose metabolism. J. Biol Chem 1980;255:9900-6.
[15] Malphettes L, Freyvert Y, Chang J, et al. Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol Bioeng 2010;106:774-83.
[16] Yurchenco PD, Atkinson PH. Equilibration of fucosyl glycoprotein pools in HeLa cells. Biochemistry 1977;16:944-53.
[17] Yurchenco PD, Atkinson PH. Fucosyl-glycoprotein and precursor polls in HeLa cells. Biochemistry 1975;14:3107-14.

Chapter 14

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•The interaction Fc/FcRn protects IgGs from catabolism and from being marked for degradation.
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[11] Peters RT, Low SC, Kamphaus GD, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 2010;115:2057-64.
•• Synthesis and characterization of the hybrid proteins comprising human FIX and the constant region, including the Fc domain, of one or two heavy chain(s) of human IgG (rFIXFc). The half-life of the clotting activity of rFIXFc is 3- to 4-fold longer than that of rFIX.
[12] Lin HF, Maeda N, Smithies O, et al. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood 1997;90:3962-6.
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[15] Bitonti AJ, Dumont JA. Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway. Adv Drug Deliv Rev 2006;58:1106-18.
•• FcRn can be harnessed to noninvasively deliver bioactive proteins into the systemic circulation in therapeutic quantities.
[16] Taupin P. Ex vivo fucosylation of stem cells to improve engraftment: WO2004094619. Expert Opin Ther Pat 2010;20:1265-9.
[17] Taupin P. Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment. Therapy 2010;7:703-15.
[18] Taupin P. Antibodies against CD20 (Rituximab) for treating multiple sclerosis: US20100233121. Expert Opin Ther Pat 2011;21:111-4.
[19] Napolitano LM. Scope of the problem: epidemiology of anemia and use of blood transfusions in critical care. Crit Care 2004;8:S1-8.

Chapter 15

[1] Taupin P. Derivation of embryonic stem cells for cellular therapy: Challenges and new strategies. Med Sci Monit 2006;12:RA75-8.
[2] Thomson JA, Kalishman J, Golos TG, et al. Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci USA 1995;92:7844-8.
[3] Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-7. Erratum in: Science 1998;282:1827.
••First report of the derivation and long-term propagation of ESCs from human blastocysyts.
[4] Taupin P. Stem cells engineering for cell-based therapy. J Neur Eng 2007;4:R59-63.
[5] Hao J, Zhu W, Sheng C, et al. Human parthenogenetic embryonic stem cells: one potential resource for cell therapy. Sci China C Life Sci 2009;52:599-602.
[6] Taupin P. Autologous transplantation in the central nervous system. Ind J Med Res 2006;124:613-18.
[7] Pashaiasl M, Khodadadi K, Holland MK, et al. The efficient generation of cell lines from bovine parthenotes. Cell Reprogram 2010;12:571-9.
[8] Sumer H, Liu J, Tat P, et al. Somatic cell nuclear transfer: pros and cons. J Stem Cells 2009;4:85-93.
[9] Shi Y. Induced pluripotent stem cells, new tools for drug discovery and new hope for stem cell therapies. Curr Mol Pharmacol 2009;2:15-8.
[10] Taupin P. Adult neural stem cells, neurogenic niches and cellular therapy. Stem Cell Rev 2006;2:213-19.
[11] Taupin P. Very small embryonic-like stem cells for regenerative medicine: WO2010039241. Exp Opin Ther Patents 2010;20:1103-6.
•Very small embryonic-like stem cells are reported pluripotent stem cells.
[12] Huang J, Okuka M, Wang F, et al. Generation of pluripotent stem cells from eggs of aging mice. Aging Cell 2010;9:113-25.
[13] Brevini TA, Pennarossa G, deEguileor M, et al. Parthenogenetic cell lines: an unstable equilibrium between pluripotency and malignant transformation. Curr Pharm Biotechnol 2011;12:206-12.
•Potential of pESCs for tumor formation.
[14] Taupin P. Stem cells from non-viable versus post-mortem tissues. Med Sci Monit 2007;13:LE1-1
[15] Taupin P. Adult neurogenesis and neural stem cells as a model for the discovery and development of novel drugs. Expert Opinion On Drug Discovery. 2010;5:921-5.
[16] Taupin P. Adult neurogenesis, neural stem cells and Alzheimer’s disease: developments, limitations, problems and promises. Current Alzheimer Research 2009;6:461-70.

Chapter 16

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Chapter 17

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Chapter 18

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Conclusion 1

[1] Taupin P, Gage FH: Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neurosci Res. 2002; 69(6): 745-749.
[2] Duan X, Kang E, Liu CY, et al.: Development of neural stem cell in the adult brain. Curr Opin Neurobiol. 2008; 18(1): 108-115.
[3] Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al.: Neurogenesis in the adult human hippocampus. Nat Med. 1998; 4(11): 1313-1317.
[4] Curtis MA, Kam M, Nannmark U, et al.: Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science. 2007; 315(5816): 1243-1249.
[5] Taupin P: Adult neural stem cells, neurogenic niches and cellular therapy. Stem Cell Rev. 2006; 2(3): 213-220.
[6] Mitsiadis TA, Barrandon O, Rochat A, et al.: Stem cell niches in mammals. Exp Cell Res. 2007; 313(16): 3377-3385.
[7] Taupin P: Adult neural stem cells from promise to treatment: The road ahead. J Neurodegener Regene. 2008; 1(1): 7-8.
[8] Parent JM, Yu TW, Leibowitz RT, et al.: Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997; 17(10): 3727-3738.
[9] Gould E, Beylin A, Tanapat P, et al.: Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999; 2(3): 260-265.
[10] Malberg JE, Eisch AJ, Nestler EJ, et al.: Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000; 20(24): 9104-9110.
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[25] Taupin P: Adult neurogenesis and drug therapy. Cent Nerv Syst. Agents Med Chem. 2008; 8: 198-202.
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[39] Taupin P: Fourteen compounds and their derivatives for the treatment of diseases and injuries characterized by reduced neurogenesis and neurodegeneration. Expert Opin Ther Pat. 2009; 19(4): 541-547.
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Conclusion 2

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