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Stem Cells and Cell Replacement Therapy for Parkinson's Disease

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Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 73))

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder caused by a progressive degeneration of the midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) that predominantly affects the ventral population projecting to the dorsal striatum and leads to a gradual dysfunction of the motor system. There is currently no cure for PD. Pharmacological and surgical (e.g. deep brain stimulation) interventions can alleviate some of the symptoms, but lose their efficacy over time. The distinct loss of DA neurons in the SN offers the opportunity to assay neuronal cell replacement, and the clinical transplantation of fetal midbrain neuroblasts in PD patients has shown that this approach is feasible. However, there are multiple problems associated with the use of fetus-derived material, including limited availability. DA neurons derived from stem cells (SC) represent an alternative and unlimited cell source for cell replacement therapies. Currently, human pluripotent SC, such as embryonic (ES), and most recently, induced pluripotent stem cells (iPS), and multipotent (tissue-specific) adult SC are available, although the methodology for a reliable and efficient production of DA neurons necessary for biomedical applications is still underdeveloped. Here, we discuss some essentials for SC and SC-derived DA neurons to become therapeutic agents.

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Abbreviations

6–OHDA:

6–hydroxydopamine

AADC:

Aromatic L-amino acid decarboxylase

BMP:

Bone morphogenic protein

DA:

Dopamine

DAT:

Dopamine transporter

ESC:

Embryonic stem cells

FACS:

Fluorescent activated cell sorting

FGF:

Fibroblast growth factor

GDNF:

Glial cell line-derived neurotrophic factor

iPS:

Induced pluripotent stem cells

MPTP:

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

PD:

Parkinson’s disease

SC:

Stem cells

SHH:

Sonic hedgehog

SNc:

Substantia nigra, pars compacta

SNCT:

Somatic nuclear cell transfer

SVZ:

Subventricular zone

TGF:

Transforming growth factor

TH:

Tyrosine hydroxylase

VMAT-2:

Vesicular monoamine transporter-2

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Authors and Affiliations

  1. Department of Psychiatry, McLean Hospital, Harvard Medical School, MRC 223 115 Mill Street, Belmont, 02478, MA, USA

    K.-C. Sonntag

  2. Laboratory of Stem Cells and Neurorepair, Fundacion Inbiomed, Paseo Mikeletegi 61, San Sebastian, 20009, Spain

    F. Simunovic

Authors
  1. K.-C. Sonntag
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  2. F. Simunovic
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  3. R. Sanchez-Pernaute
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Correspondence to K.-C. Sonntag .

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Editors and Affiliations

  1. Fac. Medicina e Chirurgia, Università di Palermo, Corso Tukory 129, Palermo, 90134, Italy

    Giuseppe Giovanni

  2. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Vincenzo Di Matteo

  3. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Ennio Esposito

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Sonntag, KC., Simunovic, F., Sanchez-Pernaute, R. (2009). Stem Cells and Cell Replacement Therapy for Parkinson's Disease. In: Giovanni, G., Di Matteo, V., Esposito, E. (eds) Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra. Journal of Neural Transmission. Supplementa, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-211-92660-4_24

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