Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model

Emily W. Baker; Simon R. Platt; Vivian W. Lau; Harrison E. Grace; Shannon P. Holmes; Liya Wang; Kylee Jo Duberstein; Elizabeth W. Howerth; Holly A. Kinder; Steve L. Stice; David C. Hess; Hui Mao; Franklin D. West

doi:10.1038/s41598-017-10406-x

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model

Emily W. Baker, Simon R. Platt, Vivian W. Lau, Harrison E. Grace, Shannon P. Holmes, Liya Wang, Kylee Jo Duberstein, Elizabeth W. Howerth, Holly A. Kinder, Steve L. Stice, David C. Hess, Hui Mao, Franklin D. West

Neurology

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

Abstract

Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.

Original language	English (US)
Article number	10075
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-10406-x
State	Published - Dec 1 2017

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Baker, E. W., Platt, S. R., Lau, V. W., Grace, H. E., Holmes, S. P., Wang, L., Duberstein, K. J., Howerth, E. W., Kinder, H. A., Stice, S. L., Hess, D. C., Mao, H., & West, F. D. (2017). Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model. Scientific reports, 7(1), Article 10075. https://doi.org/10.1038/s41598-017-10406-x

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title = "Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model",

abstract = "Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.",

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doi = "10.1038/s41598-017-10406-x",

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AU - Holmes, Shannon P.

AU - Wang, Liya

AU - Duberstein, Kylee Jo

AU - Howerth, Elizabeth W.

AU - Kinder, Holly A.

AU - Stice, Steve L.

AU - Hess, David C.

AU - Mao, Hui

AU - West, Franklin D.

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AB - Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.

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Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model

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