Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke

Robin L. Webb, Erin E. Kaiser, Brian J. Jurgielewicz, Samantha Spellicy, Shelley L. Scoville, Tyler A. Thompson, Raymond L. Swetenburg, David C. Hess, Franklin D. West, Steven L. Stice

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background and Purpose-Recent work from our group suggests that human neural stem cell-derived extracellular vesicle (NSC EV) treatment improves both tissue and sensorimotor function in a preclinical thromboembolic mouse model of stroke. In this study, NSC EVs were evaluated in a pig ischemic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model. Methods-Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS treatment was administered intravenously at 2, 14, and 24 hours post-MCAO. NSC EV effects on tissue level recovery were evaluated via magnetic resonance imaging at 1 and 84 days post-MCAO. Effects on functional recovery were also assessed through longitudinal behavior and gait analysis testing. Results-NSC EV treatment was neuroprotective and led to significant improvements at the tissue and functional levels in stroked pigs. NSC EV treatment eliminated intracranial hemorrhage in ischemic lesions in NSC EV pigs (0 of 7) versus control pigs (7 of 8). NSC EV-treated pigs exhibited a significant decrease in cerebral lesion volume and decreased brain swelling relative to control pigs 1-day post-MCAO. NSC EVs significantly reduced edema in treated pigs relative to control pigs, as assessed by improved diffusivity through apparent diffusion coefficient maps. NSC EVs preserved white matter integrity with increased corpus callosum fractional anisotropy values 84 days post-MCAO. Behavior and mobility improvements paralleled structural changes as NSC EV-treated pigs exhibited improved outcomes, including increased exploratory behavior and faster restoration of spatiotemporal gait parameters. Conclusions-This study demonstrated for the first time that in a large animal model novel NSC EVs significantly improved neural tissue preservation and functional levels post-MCAO, suggesting NSC EVs may be a paradigm changing stroke therapeutic.

Original languageEnglish (US)
Pages (from-to)1248-1256
Number of pages9
JournalStroke
Volume49
Issue number5
DOIs
StatePublished - Jan 1 2018

Fingerprint

Neural Stem Cells
Swine
Middle Cerebral Artery Infarction
Stroke
Gait
Animal Models
Tissue Preservation
Extracellular Vesicles
Exploratory Behavior
Intracranial Hemorrhages
Corpus Callosum
Anisotropy
Brain Edema
Therapeutics
Edema
Magnetic Resonance Imaging

Keywords

  • Brain ischemia
  • Extracellular vesicles
  • Magnetic resonance imaging
  • Stroke
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Webb, R. L., Kaiser, E. E., Jurgielewicz, B. J., Spellicy, S., Scoville, S. L., Thompson, T. A., ... Stice, S. L. (2018). Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke, 49(5), 1248-1256. https://doi.org/10.1161/STROKEAHA.117.020353

Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. / Webb, Robin L.; Kaiser, Erin E.; Jurgielewicz, Brian J.; Spellicy, Samantha; Scoville, Shelley L.; Thompson, Tyler A.; Swetenburg, Raymond L.; Hess, David C.; West, Franklin D.; Stice, Steven L.

In: Stroke, Vol. 49, No. 5, 01.01.2018, p. 1248-1256.

Research output: Contribution to journalArticle

Webb, RL, Kaiser, EE, Jurgielewicz, BJ, Spellicy, S, Scoville, SL, Thompson, TA, Swetenburg, RL, Hess, DC, West, FD & Stice, SL 2018, 'Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke', Stroke, vol. 49, no. 5, pp. 1248-1256. https://doi.org/10.1161/STROKEAHA.117.020353
Webb RL, Kaiser EE, Jurgielewicz BJ, Spellicy S, Scoville SL, Thompson TA et al. Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke. 2018 Jan 1;49(5):1248-1256. https://doi.org/10.1161/STROKEAHA.117.020353
Webb, Robin L. ; Kaiser, Erin E. ; Jurgielewicz, Brian J. ; Spellicy, Samantha ; Scoville, Shelley L. ; Thompson, Tyler A. ; Swetenburg, Raymond L. ; Hess, David C. ; West, Franklin D. ; Stice, Steven L. / Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. In: Stroke. 2018 ; Vol. 49, No. 5. pp. 1248-1256.
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abstract = "Background and Purpose-Recent work from our group suggests that human neural stem cell-derived extracellular vesicle (NSC EV) treatment improves both tissue and sensorimotor function in a preclinical thromboembolic mouse model of stroke. In this study, NSC EVs were evaluated in a pig ischemic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model. Methods-Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS treatment was administered intravenously at 2, 14, and 24 hours post-MCAO. NSC EV effects on tissue level recovery were evaluated via magnetic resonance imaging at 1 and 84 days post-MCAO. Effects on functional recovery were also assessed through longitudinal behavior and gait analysis testing. Results-NSC EV treatment was neuroprotective and led to significant improvements at the tissue and functional levels in stroked pigs. NSC EV treatment eliminated intracranial hemorrhage in ischemic lesions in NSC EV pigs (0 of 7) versus control pigs (7 of 8). NSC EV-treated pigs exhibited a significant decrease in cerebral lesion volume and decreased brain swelling relative to control pigs 1-day post-MCAO. NSC EVs significantly reduced edema in treated pigs relative to control pigs, as assessed by improved diffusivity through apparent diffusion coefficient maps. NSC EVs preserved white matter integrity with increased corpus callosum fractional anisotropy values 84 days post-MCAO. Behavior and mobility improvements paralleled structural changes as NSC EV-treated pigs exhibited improved outcomes, including increased exploratory behavior and faster restoration of spatiotemporal gait parameters. Conclusions-This study demonstrated for the first time that in a large animal model novel NSC EVs significantly improved neural tissue preservation and functional levels post-MCAO, suggesting NSC EVs may be a paradigm changing stroke therapeutic.",
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AU - Thompson, Tyler A.

AU - Swetenburg, Raymond L.

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KW - White matter

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