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

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


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.


Stem cells Ischaemic stroke Noninvasive imaging Gene therapy Regenerative medicine Immunomodulation 



α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid




Adipose-derived stem cell


Adenosine triphosphate


Blood-brain barrier


Brain-derived neurotrophic factor


Basic fibroblast growth factor


Bioluminescence imaging


Bone marrow-derived mononuclear cells


Bone marrow-derived MSC


C-C chemokine receptor type 2


Computed tomography


C-X-C chemokine receptor type 4


Danger associated molecular pattern molecules


Dental pulp stem cell


Endothelial cells


Extracellular matrix


Epidermal growth factor


Embryonic stem cell


Extracellular vesicles


Fibroblast growth factor


Fluorescence imaging


Glial-derived neurotrophic factor


Glial fibrillary acid protein


Human embryonic stem cell


Hepatocyte growth factor


Intercellular Adhesion Molecule 1


Indoleamine 2,3-dioxygenase




Insulin-like growth factor 1




Induced pluripotent stem cell


Middle cerebral artery occlusion


Monocyte chemotactic protein 1


Major histocompatibility complex


Mixed lymphocyte reaction


Matrix metalloproteinase


Magnetic resonance imaging


Mesenchymal stem cell


Nuclear factor kappa B


Nerve growth factor

NK cells

Natural killer cells


N-methyl-D-aspartic acid


Nitric Oxide


Neural stem cell


Oxygen-glucose deprivation


Platelet-derived growth factor BB


Positron emission tomography


Prostaglandin E2


Reactive oxygen species


stromal cell-derived factor 1 α


Subgranular zone


Single-photon emission computed tomography


Superparamagnetic iron oxide


Signal transducer and activator of transcription 3


Subventricular zone


Transforming growth factor beta


Tissue inhibitor of metalloproteinase


Tumour necrosis factor alfa


Regulatory T cell


Vascular endothelial growth factor



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
    Email author
  • 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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