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Review
. 2021 Jul 19;22(14):7703.
doi: 10.3390/ijms22147703.

Neural Stem Cells for Early Ischemic Stroke

Milton H Hamblin  1 , Jean-Pyo Lee  2   3
Affiliations
Review

Neural Stem Cells for Early Ischemic Stroke

Milton H Hamblin et al. Int J Mol Sci. .

Abstract

Clinical treatments for ischemic stroke are limited. Neural stem cell (NSC) transplantation can be a promising therapy. Clinically, ischemia and subsequent reperfusion lead to extensive neurovascular injury that involves inflammation, disruption of the blood-brain barrier, and brain cell death. NSCs exhibit multiple potentially therapeutic actions against neurovascular injury. Currently, tissue plasminogen activator (tPA) is the only FDA-approved clot-dissolving agent. While tPA's thrombolytic role within the vasculature is beneficial, tPA's non-thrombolytic deleterious effects aggravates neurovascular injury, restricting the treatment time window (time-sensitive) and tPA eligibility. Thus, new strategies are needed to mitigate tPA's detrimental effects and quickly mediate vascular repair after stroke. Up to date, clinical trials focus on the impact of stem cell therapy on neuro-restoration by delivering cells during the chronic stroke stage. Also, NSCs secrete factors that stimulate endogenous repair mechanisms for early-stage ischemic stroke. This review will present an integrated view of the preclinical perspectives of NSC transplantation as a promising treatment for neurovascular injury, with an emphasis on early-stage ischemic stroke. Further, this will highlight the impact of early sub-acute NSC delivery on improving short-term and long-term stroke outcomes.

Keywords: blood-brain barrier; matrix metalloproteinases; neural stem cells; stroke; tissue plasminogen activator; transplantation.

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Conflict of interest statement

The authors have no conflict of interest to disclose.

Figures

Figure 1
Figure 1
Schematic diagram of NSC derivation through diverse methods and sources. NSCs can be directly extracted from neural tissue and expanded in vitro. Also, NSCs can be reprogrammed from iPSCs or ESCs by specific combinations of differentiation factors. Further, NSCs can be generated by direct conversion of somatic cells omitting the iPSC derivation step. ICM, inner cell mass.
Figure 2
Figure 2
Schematic diagram of NSC delivery illustrating multiple therapeutic mechanisms in ischemic stroke. NSCs can differentiate into functional neurons in the stroke brain and possess pleotropic bystander effects. These bystander effects include attenuation of blood-brain barrier (BBB) disruption, increased angiogenesis, and modulation of immune responses after ischemic stroke. ECs, endothelial cells.
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