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Sci Rep. 2017 Aug 30;7(1):10075. doi: 10.1038/s41598-017-10406-x.

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

Author information

1
Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA.
2
Department of Animal and Dairy Science, University of Georgia, Athens, GA, 30602, USA.
3
Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, 30602, USA.
4
Department of Veterinary Biosciences & Diagnostic Imaging, University of Georgia, Athens, GA, 30602, USA.
5
Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, 30329, USA.
6
Department of Pathology, University of Georgia, Athens, GA, 30602, USA.
7
Department of Neurology, Augusta University, Augusta, GA, 30912, USA.
8
Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA. westf@uga.edu.
9
Department of Animal and Dairy Science, University of Georgia, Athens, GA, 30602, USA. westf@uga.edu.

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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