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Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells

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Abstract

Motor neuron diseases (MNDs) are a group of neurological disorders that selectively affect motor neurons. There are currently no cures or efficacious treatments for these diseases. In recent years, significant developments in stem cell research have been applied to MNDs, particularly regarding neuroprotection and cell replacement. However, a consistent source of motor neurons for cell replacement is required. Human embryonic stem cells (hESCs) could provide an inexhaustible supply of differentiated cell types, including motor neurons that could be used for MND therapies. Recently, it has been demonstrated that induced pluripotent stem (iPS) cells may serve as an alternative source of motor neurons, since they share ES characteristics, self-renewal, and the potential to differentiate into any somatic cell type. In this review, we discuss several reproducible methods by which hESCs or iPS cells are efficiently isolated and differentiated into functional motor neurons, and possible clinical applications.

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Abbreviations

MNDs:

Motor neuron diseases

hESCs:

Human embryonic stem cells

hiPSC:

Human induced pluripotent stem cells

CNS:

Central nervous system

ALS:

Amyotrophic lateral sclerosis

SMA:

Spinal muscular atrophy

NE:

Neuroepithelial

EBs:

Embryoid bodies

MEF:

Mouse embryonic fibroblasts

hSCs:

Human stem cells

bFGF:

Fibroblast growth factor

RA:

Retinoic acid

Shh:

Sonic hedgehog

cAMP:

Cyclic adenosine monophosphate

BDNF:

Brain-derived neurotrophic factor

GDNF:

Glial-derived neurotrophic factor

p75-NGFR:

Nerve growth factor receptor

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Acknowledgments

The financial support of the following research grants to S.C. and G.P.C. is gratefully acknowledged: FSMA and SMA Europe Grant, Telethon grant: GGP09107, “Neuroprotection in Spinal Muscular Atrophy (SMA) using neural stem cells as a therapeutic approach.” We wish to thank the Associazione Amici del Centro Dino Ferrari for their support. We wish to thank Dr. Serena Ghezzi for her help in graphic illustration.

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Authors and Affiliations

  1. Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation, IRCCS Foundation Ca’Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy

    M. Nizzardo, C. Simone, M. Falcone, G. Riboldi, G. P. Comi & S. Corti

  2. Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy

    G. Riboldi, G. P. Comi & S. Corti

  3. IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy

    F. Locatelli

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  1. M. Nizzardo
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  2. C. Simone
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  3. M. Falcone
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  4. F. Locatelli
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Correspondence to M. Nizzardo.

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Nizzardo, M., Simone, C., Falcone, M. et al. Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells. Cell. Mol. Life Sci. 67, 3837–3847 (2010). https://doi.org/10.1007/s00018-010-0463-y

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