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

  • Pascal Gervois
  • Yörg Dillen
  • Tim Vangansewinkel
  • Petra Hilkens
  • Ronald B. Driesen
  • Greet Merckx
  • Melissa Lo Monaco
  • Jessica Ratajczak
  • Annelies Bronckaers
  • Ivo Lambrichts
  • Esther Wolfs
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

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.

Keywords

Stem cells Ischaemic stroke Noninvasive imaging Gene therapy Regenerative medicine Immunomodulation 

Abbreviation

AMPA

α-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-γ

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-κB

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-1α

stromal cell-derived factor 1 α

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-β

Transforming growth factor beta

TIMP

Tissue inhibitor of metalloproteinase

TNF-α

Tumour necrosis factor alfa

Treg

Regulatory T cell

VEGF

Vascular endothelial growth factor

Notes

Acknowledgements

Pascal Gervois, Esther Wolfs, Jessica Ratajczak, Tim Vangansewinkel, Petra Hilkens, Yörg Dillen and Annelies Bronckaers are funded by Fonds Wetenschappelijk Onderzoek Vlaanderen by grants 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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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Pascal Gervois
    • 1
  • Yörg Dillen
    • 1
  • Tim Vangansewinkel
    • 1
  • Petra Hilkens
    • 1
  • Ronald B. Driesen
    • 1
  • Greet Merckx
    • 1
  • Melissa Lo Monaco
    • 1
  • Jessica Ratajczak
    • 1
  • Annelies Bronckaers
    • 1
  • Ivo Lambrichts
    • 1
  • Esther Wolfs
    • 1
  1. 1.Morphology Research Group, Biomedical Research InstituteHasselt UniversityDiepenbeekBelgium

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