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Interdisciplinary Advances Towards Understanding and Enhancing the Therapeutic Potential of Stem Cell-Based Therapies for Ischaemic Stroke

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Book cover Cellular and Molecular Approaches to Regeneration and Repair

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

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Abstract

Worldwide, stroke is the second single most common cause of death and is a major cause of permanent disability. Moreover, the highest incidence of these pathologies is observed in the elderly, increasing the socioeconomic burden in an aging population. Current available therapies lead to insufficient functional improvement or are not applicable to all patients. This stresses the urgent need for alternative strategies in treating stroke patients, for example cell-based therapies. These cells showed great preclinical potential although the underlying therapeutic mechanisms, preferential route of administration and most suitable stem cell-subtype are unknown. Mechanisms of action include neuroprotection, cell replacement, neurogenesis, immunomodulation and the promotion of both neuroplasticity and angiogenesis in damaged central nervous system regions. Moreover, stem cells have been genetically engineered to enhance their beneficial effects after transplantation. Additionally, noninvasive imaging can be used to provide detailed spatial and functional information on the donor cell fate and the response of the host microenvironment. This chapter provides an overview of recent advances in (bio-)medical research using or manipulating stem cell-based therapies for ischaemic stroke with a focus on their neuroprotective, neuroregenerative and immunomodulatory properties. Additionally, the use of noninvasive imaging to allow temporospatial evaluation of stem cell fate following transplantation in animal stroke models will be discussed.

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Abbreviations

AMPA:

Ī±-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

Ang-1:

Angiopoietin-1

ASC:

Adipose-derived stem cell

ATP:

Adenosine triphosphate

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

BLI:

Bioluminescence imaging

BM-MNC:

Bone marrow-derived mononuclear cells

BMMSC:

Bone marrow-derived MSC

CCR2:

C-C chemokine receptor type 2

CT:

Computed tomography

CXCR4:

C-X-C chemokine receptor type 4

DAMPs:

Danger associated molecular pattern molecules

DPSC:

Dental pulp stem cell

EC:

Endothelial cells

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

ESC:

Embryonic stem cell

EVs:

Extracellular vesicles

FGF:

Fibroblast growth factor

FLI:

Fluorescence imaging

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acid protein

hESC:

Human embryonic stem cell

HGF:

Hepatocyte growth factor

ICAM-1:

Intercellular Adhesion Molecule 1

IDO:

Indoleamine 2,3-dioxygenase

IFN-Ī³:

Interferon-gamma

IGF-1:

Insulin-like growth factor 1

IL:

Interleukin

iPSC:

Induced pluripotent stem cell

MCAO:

Middle cerebral artery occlusion

MCP-1:

Monocyte chemotactic protein 1

MHC:

Major histocompatibility complex

MLR:

Mixed lymphocyte reaction

MMP:

Matrix metalloproteinase

MRI:

Magnetic resonance imaging

MSC:

Mesenchymal stem cell

NF-ĪŗB:

Nuclear factor kappa B

NGF:

Nerve growth factor

NK cells:

Natural killer cells

NMDA:

N-methyl-D-aspartic acid

NO:

Nitric Oxide

NSC:

Neural stem cell

OGD:

Oxygen-glucose deprivation

PDGF-BB:

Platelet-derived growth factor BB

PET:

Positron emission tomography

PGE2:

Prostaglandin E2

ROS:

Reactive oxygen species

SDF-1Ī±:

stromal cell-derived factor 1 Ī±

SGZ:

Subgranular zone

SPECT:

Single-photon emission computed tomography

SPIO:

Superparamagnetic iron oxide

STAT3:

Signal transducer and activator of transcription 3

SVZ:

Subventricular zone

TGF-Ī²:

Transforming growth factor beta

TIMP:

Tissue inhibitor of metalloproteinase

TNF-Ī±:

Tumour necrosis factor alfa

Treg:

Regulatory T cell

VEGF:

Vascular endothelial growth factor

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Acknowledgements

Pascal Gervois,Ā Esther Wolfs, Jessica Ratajczak, Tim Vangansewinkel, Petra Hilkens, Yƶrg Dillen and Annelies Bronckaers are funded by Fonds Wetenschappelijk OnderzoekĀ Vlaanderen by grantsĀ 12U7718N, G0A7514N, G089213N, G029112N, 12D8516N, 1134717N and 1508015N respectively. Greet Merckx and Melissa Lo Monaco are funded by Bijzonder Onderzoeksfonds grants BOF16DOC06 and BOF16DOCNA02 respectively.

Conflict of Interest: The authors declare that they have no conflict of interest.

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  1. Morphology Research Group, Biomedical Research Institute, Hasselt University, Agoralaan Building C, Diepenbeek, 3590, Belgium

    Pascal Gervois,Ā Yƶrg Dillen,Ā Tim Vangansewinkel,Ā Petra Hilkens,Ā Ronald B. Driesen,Ā Greet Merckx,Ā Melissa Lo Monaco,Ā Jessica Ratajczak,Ā Annelies Bronckaers,Ā Ivo LambrichtsĀ &Ā Esther Wolfs

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  1. Pascal Gervois
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  1. Department of Neurology & Neurosurgery, Cedars-Sinai Medical Center, AHSP, Los Angeles, California, USA

    Paul A. Lapchak

  2. Department of Physiology, Loma Linda University, Loma Linda, California, USA

    John H. Zhang

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Gervois, P. et al. (2018). Interdisciplinary Advances Towards Understanding and Enhancing the Therapeutic Potential of Stem Cell-Based Therapies for Ischaemic Stroke. In: Lapchak, P., Zhang, J. (eds) Cellular and Molecular Approaches to Regeneration and Repair. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-66679-2_2

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