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Repair of the CNS Using Endogenous and Transplanted Neural Stem Cells

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Neurogenesis and Neural Plasticity

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 15))

Abstract

Restoration of the damaged central nervous system is a vast challenge. However, there is a great need for research into this topic, due to the prevalence of central nervous system disorders and the devastating impact they have on people’s lives. A number of strategies are being examined to achieve this goal, including cell replacement therapy, enhancement of endogenous plasticity and the recruitment of endogenous neurogenesis. The current chapter reviews this topic within the context of Parkinson’s disease, Huntington’s disease and stroke. For each disease exogenous cell therapies are discussed including primary (foetal) cell transplants, neural stem cells, induced pluripotent stem cells and marrow stromal cells. This chapter highlights the different mechanistic approaches of cell replacement therapy versus cells that deliver neurotropic factors, or enhance the endogenous production of these factors. Evidence of exogenously transplanted cells functionally integrating into the host brain, replacing cells, and having a behavioural benefit are discussed, along with the ability of some cell sources to stimulate endogenous neuroprotective and restorative events. Alongside exogenous cell therapy, the role of endogenous neurogenesis in each of the three diseases is outlined and methods to enhance this phenomenon are discussed.

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Abbreviations

6-OHDA:

6-hydroxydopamine

BBB:

Blood–brain barrier

BDNF:

Brain-derived neurotrophic factor

bNGF:

Nerve growth factor beta

DA:

Dopamine

DAergic:

Dopaminergic

ESCs:

Embryonic stem cells

FGF:

Fibroblast growth factor

GDNF:

Glial cell line-derived growth factor

GE:

Ganglionic eminence

HD:

Huntington’s disease

iNs:

Induced neural stem cells

iPSCs:

Induced pluripotent stem cells

L-DOPA:

L-dihydroxyphenylalanine

MPTP:

1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine

MSCs:

Mesenchymal stem cells

NSCs:

Neural stem cells

PD:

Parkinson’s disease

SGZ:

Subgranular zone

SN:

Substantia nigra

SVZ:

Subventricular zone

TH:

Tyrosine hydroxylase

VEGF:

Vascular endothelial growth factor

VM:

Ventral mesencephalon

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Authors and Affiliations

  1. School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK

    R. C. Trueman

  2. Hannover Medical School (MHH), Institute of Neuroanatomy, Carl-Neuberg-Str, 30623, Hannover, Germany

    A. Klein

  3. The Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK

    H. S. Lindgren, M. J. Lelos & S. B. Dunnett

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  1. R. C. Trueman
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  2. A. Klein
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  5. S. B. Dunnett
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  1. , INSERM 930, Faculté des Sciences, Parc Grandmont, Tours, 37200, France

    Catherine Belzung

  2. Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

    Peter Wigmore

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Trueman, R.C., Klein, A., Lindgren, H.S., Lelos, M.J., Dunnett, S.B. (2012). Repair of the CNS Using Endogenous and Transplanted Neural Stem Cells. In: Belzung, C., Wigmore, P. (eds) Neurogenesis and Neural Plasticity. Current Topics in Behavioral Neurosciences, vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2012_223

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