Cited by 205Neurogenesis and neuroplasticity mechanismsMesenchymal stem cell researchAcute Ischemic Stroke Management

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Neural stem cell therapy for subacute and chronic ischemic stroke

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Boese, Austin C., Le, Quan-Son Eric, Pham, Dylan, Hamblin, Milton H., Lee, Jean-Pyo·2018·Stem Cell Research & Therapy

DOI 10.1186/s13287-018-0913-2PMC PMC5998588

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Abstract

Neural stem cells (NSCs) play vital roles in brain homeostasis and exhibit a broad repertoire of potentially therapeutic actions following neurovascular injury. One such injury is stroke, a worldwide leading cause of death and disability. Clinically, extensive injury from ischemic stroke results from ischemia-reperfusion (IR), which is accompanied by inflammation, blood-brain barrier (BBB) damage, neural cell death, and extensive tissue loss. Tissue plasminogen activator (tPA) is still the only US Food and Drug Administration-approved clot-lysing agent. Whereas the thrombolytic role of tPA within the vasculature is beneficial, the effects of tPA (in a non-thrombolytic role) within the brain parenchyma have been reported as harmful. Thus, new therapies are needed to reduce the deleterious side effects of tPA and quickly facilitate vascular repair following stroke. The Stroke Treatment Academic Industry Roundtable (STAIR) recommends that stroke therapies "focus on drugs/devices/treatments with multiple mechanisms of action and that target multiple pathways". Thus, based on multifactorial ischemic cascades in various stroke stages, effective stroke therapies need to focus on targeting and ameliorating early IR injury as well as facilitating angiogenesis, neurogenesis, and neurorestorative mechanisms following stroke. This review will discuss the preclinical perspectives of NSC transplantation as a promising treatment for neurovascular injury and will emphasize both the subacute and chronic phase of ischemic stroke.

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Fig. 1 Schematic diagram of NSC generation via multiple methods. NSCs can be extracted directly from neurogenic niches, including the subgranular zone (SGZ) of the hippocampal dentate gyrus and subventricular zone (SVZ) of the lateral ventricles, from adult or fetal neural tissue and expanded in vitro. NSCs can be reprogrammed from patient-derived induced pluripotent stem cells by using combinations of specific transcription factors, small molecules, microRNAs, plasmids, and other morphogens. In addition, NSCs can be generated from blastocyst-derived embryonic stem cells by using specific combinations of differentiation factors, such as morphogens and extracellular matrix (ECM) proteins. Abbreviation: NSC neural stem cellCC BY · PubMed Central

Fig. 2 Schematic diagram of NSC transplantation illustrating multiple therapeutic benefits in ischemic stroke. Exogenous NSCs can be transplanted intravenously or directly into the damaged or penumbral parenchyma. NSCs can replace damaged neural cells in ischemic brain tissue. NSCs may also help to prevent further tissue damage in ischemic stroke through their bystander effects. These bystander effects include support of the blood-brain barrier (BBB), neurons, astrocytes, and microglia, as well as increased angiogenesis, and modulation of immune responses that result from ischemic insult. Abbreviations: EC endothelial cell, NSC neural stem cellCC BY · PubMed Central

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Authors: Boese, A. C., Le, Q.-S. E., Pham, D., Hamblin, M. H., & Lee, J.-P.
Affiliations: Tulane University (US)
Corresponding author: Lee, Jean-Pyo
ORCID: Boese, Austin C.
Le, Quan-Son Eric
Pham, Dylan
Hamblin, Milton H.
Venue: Stem Cell Research & Therapy
Publisher: Springer Science and Business Media LLC
Published: 2018-06-13
Volume: 9
Issue: 1
Pages: 154-154
ISSN: 1757-6512 (ISSN-L)
DOI: 10.1186/s13287-018-0913-2
PMC: PMC5998588
OpenAlex: W2808420239
Cited by: 205
References: 247
Citations by year: 2026: 4 · 2025: 28 · 2024: 19 · 2023: 46 · 2022: 38 · 2021: 30 · 2020: 19 · 2019: 15 · 2018: 5
FWCI: 2.18
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: Stem Cell Research & Therapy (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Louisiana Clinical and Translational Science Center
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Keywords: neural stem cell transplantation, ischemic stroke, ischemia-reperfusion injury, subacute stroke, chronic stroke, tissue plasminogen activator, blood-brain barrier disruption, neuroinflammation, angiogenesis, neurogenesis, neurovascular injury, stroke treatment
MeSH terms: Brain Ischemia, Chronic Disease, Humans, Tissue Plasminogen Activator, Stroke, Stem Cell Transplantation

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Neural stem cell therapy for subacute and chronic ischemic stroke

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