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Stem Cells in Neurological Disorders: Emerging Therapy with Stunning Hopes

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Abstract

Neurodegenerative diseases are still a challenge for researchers and clinicians due to its complexity. Traditional medicines usually do not provide sufficient protection against these diseases due to drug resistance and relapse. The discovery of the therapeutic potential of stem cells offers new opportunities for the treatment of incurable neurological diseases. Based on their biological properties, stem cells can differentiate into specific tissue type and maintain the cellular tissue/organ homeostasis in physiological and pathological conditions. Recently, it has been demonstrated that somatic cells of patients can be reprogrammed to a pluripotent state from which neural lineage cells can be derived. Potential strategies such as cell replacement therapy and gene transfer to the diseased or injured brain have opened a new line of therapeutic approach for a broad spectrum of human neurological diseases. Thus, stem cell replacement therapy for central and peripheral nervous system disorders aims at repopulating the affected neural tissue with new neurons. However, the limiting factors that have hampered the development of this promising therapeutic approach are the lack of suitable cell types for cell replacement therapy in patients suffering from neurological disorders. In this review, we have discussed the recent advances in stem cell replacement therapy with particular emphasis to neurological disorders.

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Abbreviations

DA:

Dopaminergic

ESCs:

Embryonic stem cells

iPSCs:

Induced pluripotent stem cells

iPS cells:

Induced pluripotent stem cells

ADSCs:

Adipose-derived stromal cells

BM-MSCs:

Bone marrow-derived mesenchymal stem cells

NSCs:

Neural stem cells

NGF:

Nerve growth factor

BDNF:

Brain-derived growth factor

Oct4:

Octamer-binding transcription factor 4

Mbd3:

Methyl-CpG-binding domain protein 3

NuRD:

Nucleosome remodeling and deacetylase

Ascl1:

Achaete-scute complex homolog 1

Brn2:

Brain-2

Myt1l:

Myelin transcription factor 1-like

NeuroD:

Neuronal differentiation

OLIG2:

Oligodendrocyte lineage transcription factor 2

Zic1:

Zinc finger protein of the cerebellum 1

miR-9/9*:

Bifunctional microRNA strands 9

miR-124:

MicroRNA 124

Lmx1a:

LIM homeobox transcription factor 1 alpha

Nurr1:

Nuclear receptor related 1

Pitx3:

Paired-like homeodomain 3

Foxa2:

Forkhead box A2

EN1:

Engrailed homeobox 1

Lhx3:

LIM homeobox 3

Hb9:

Homeobox 9

Isl1:

Islet 1 (ISL LIM homeobox 1)

Ngn2:

Neurogenin 2

Sox2:

Sex determining region Y box 2

Klf4:

Krüppel-like factor 4

c-Myc:

v-Myc avian myelocytomatosis viral oncogene homolog

E47/Tcf3:

Transcription factor 3

Aβ:

Amyloid-beta

APP:

Amyloid precursor protein

ASC:

Adult Stem Cells

BM-MSC:

Bone marrow mesenchymal stem cell

ChAT:

Choline-acetyltransferase

EPI-NCSC:

Epidermal neural crest stem cell

ES:

Embryonic stem cell

NGFR:

Nerve growth factor receptor

hNSC:

Human neural stem cell

mNSC:

Murine neural stem cell

UCB-MSC:

Umbilical cord blood mesenchymal stem cell

LRRK2:

Leucine-rich repeat kinase 2

PINK1:

PTEN-induced putative kinase 1

Fbxo7:

F-Box only protein 7

PSEN1:

Presenilin protein 1

PSEN2:

Presenilin protein 2

TREM2:

Triggering receptor expressed on myeloid cells 2

APP:

Amyloid precursor protein

SOD1:

Superoxide dismutase 1

VAPB:

Vesicle-associated membrane protein-associated protein B/C

TDP43:

TAR DNA-binding protein 43

C9ORF72:

Chromosome 9 open reading frame 72

FUS:

Fused in sarcoma

ABCG2:

ATP-binding cassette sub-family G member 2

CXCR4:

C-X-C chemokine receptor type 4

FGF R4:

Fibroblast growth factor receptor 4

Frizzled-9:

Frizzled class receptor 9

Glut1:

Glucose transporter 1

SSEA-1:

Stage-specific embryonic antigen 1

BLBP/FABP7:

Brain lipid binding protein (also fatty acid binding protein 7)

GLAST/SLC1A3:

Glutamate aspartate transporter or solute carrier family 1 (glial high-affinity glutamate transporter) member 3

GFAP:

Glial fibrillary acidic protein

S100B:

S100 calcium binding protein B

PAX6:

Paired box protein 6

TBR2:

T-box brain protein 2 or eomesodermin

FGF:

Fibroblast growth factor

Islet-1 and 2:

ISL LIM homeobox 1 and 2

Lhx3:

LIM/homeobox protein 3

Olig2:

Oligodendrocyte transcription factor

MOG:

Myelin oligodendrocyte glycoprotein

GalC:

Galactosylceramidase

NeuN:

Feminizing locus on X-3 Fox-3 Rbfox3, or hexaribonucleotide binding protein-3

NF-L:

Light neurofilament

NF-M:

Medium neurofilament

TH:

Tyrosine hydroxylase

GAD:

Glutamic acid decarboxylase

PSD-95:

Postsynaptic density protein 95

VAMP:

Vesicle-associated membrane proteins

EMT:

Mesenchymal to endothelial transition

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Acknowledgments

We thank our lab members for critical reading of the manuscript.

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The authors declare no conflicts of interest.

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GU wrote the manuscript; SS and RKS edited the manuscript. All authors read and approved the manuscript.

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  1. Department of Biology, City College of New York, Marshak Building, 160 Convent Avenue, New York, NY, 10031, USA

    Ghanshyam Upadhyay

  2. Kansas City VA Medical Center, 4801 Linwood Boulevard, Kansas City, MO, 66128, USA

    Sharmila Shankar & Rakesh K. Srivastava

  3. Department of Pathology, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    Sharmila Shankar

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  1. Ghanshyam Upadhyay
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Upadhyay, G., Shankar, S. & Srivastava, R.K. Stem Cells in Neurological Disorders: Emerging Therapy with Stunning Hopes. Mol Neurobiol 52, 610–625 (2015). https://doi.org/10.1007/s12035-014-8883-6

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