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

• Type of Material: Article
• Authors: Emily W. Baker, University of Georgia; Simon R. Platt, University of Georgia; Vivian W. Lau, University of Georgia; Harrison E. Grace, University of Georgia; Shannon P. Holmes, University of Georgia; Liya Wang, Emory University; Kylee Jo Duberstein, University of Georgia; Elizabeth W. Howerth, University of Georgia; Holly A. Kinder, University of Georgia; Steve L. Stice, University of Georgia; David C. Hess, Augusta University; Hui Mao, Emory University; Franklin D. West, University of Georgia
• Language: English
• Date: 2017-08-30
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2017
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-017-10406-x
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 7
• Issue: 1
• Start Page: 10075
• End Page: 10075
• Grant/Funding Information: Research reported in this publication was supported, in part, by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R01NS093314 as well as the University of Georgia Office of the Vice President for Research.
• Keywords: SUBVENTRICULAR ZONE; NEURONS; ANGIOGENESIS; TRAUMATIC BRAIN-INJURY; ENDOGENOUS NEUROGENESIS; TRANSPLANTATION; Science & Technology - Other Topics; FOCAL CEREBRAL-ISCHEMIA; WHITE-MATTER; Multidisciplinary Sciences; NEURODEGENERATIVE DISEASES; Science & Technology; RAT-BRAIN
• Research Categories: Biology, Animal Physiology; Biology, Cell

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.