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Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat

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Abstract

Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

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Acknowledgements

ILA, AKH, AS, and IS would like to acknowledge funding by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology—Samarbeidsorganet HMN-NTNU. Additionally, IS and AS acknowledge funding by the Norwegian Financial Mechanism 2009–2014 and the Czech Ministry of Education, Youth and Sports under Project Contract No. MSMT-28477/2014, Project 7F14057. The authors would like to thank Dr. Marius Widerøe for technical assistance with setting up the MR scanning parameters. Many thanks to Professors Berit Strand and Michel Modo for useful discussions.

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    Authors and Affiliations

    1. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

      Ingrid Lovise Augestad, Axel Sandvig, Asta Kristine Håberg & Ioanna Sandvig

    2. Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

      Axel Karl Gottfrid Nyman

    3. Department of Biotechnology, Faculty of Natural Sciences and Technology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

      Alex Ignatius Costa

    4. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK

      Susan Carol Barnett

    5. Division of Pharmacology and Clinical Neurosciences, Department of Neurosurgery and Clinical Neurophysiology, Umeå University, Umeå, Sweden

      Axel Sandvig

    6. Department of Radiology and Nuclear Medicine, St. Olavs, Trondheim University Hospital, Trondheim, Norway

      Asta Kristine Håberg

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    1. Ingrid Lovise Augestad
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    Ingrid Lovise Augestad and Axel Karl Gottfrid Nyman have contributed equally to this work.

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    Augestad, I.L., Nyman, A.K.G., Costa, A.I. et al. Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat. Neurochem Res 42, 1599–1609 (2017). https://doi.org/10.1007/s11064-016-2098-3

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