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Neural Stem Cells for Early Ischemic Stroke

期刊

出版社

MDPI
DOI: 10.3390/ijms22147703

关键词

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

资金

  1. National Institute of Neurological Disorders and Stroke [R01NS110370]

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Neural stem cell transplantation shows promise in treating ischemic stroke by potentially therapeutic actions against neurovascular injury. By secreting factors that stimulate endogenous repair mechanisms, NSCs can promote self-recovery in early-stage ischemic stroke and improve short-term and long-term stroke outcomes.
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.

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