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Connectomics of Morphogenetically Engineered Neurons as a Predictor of Functional Integration in the Ischemic Brain
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway.
2019 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 630Article, review/survey (Refereed) Published
Abstract [en]

Recent advances in cell reprogramming technologies enable the in vitro generation of theoretically unlimited numbers of cells, including cells of neural lineage and specific neuronal subtypes from human, including patient-specific, somatic cells. Similarly, as demonstrated in recent animal studies, by applying morphogenetic neuroengineering principles in situ, it is possible to reprogram resident brain cells to the desired phenotype. These developments open new exciting possibilities for cell replacement therapy in stroke, albeit not without caveats. Main challenges include the successful integration of engineered cells in the ischemic brain to promote functional restoration as well as the fact that the underlying mechanisms of action are not fully understood. In this review, we aim to provide new insights to the above in the context of connectomics of morphogenetically engineered neural networks. Specifically, we discuss the relevance of combining advanced interdisciplinary approaches to: validate the functionality of engineered neurons by studying their self-organizing behavior into neural networks as well as responses to stroke-related pathology in vitro; derive structural and functional connectomes from these networks in healthy and perturbed conditions; and identify and extract key elements regulating neural network dynamics, which might predict the behavior of grafted engineered neurons post-transplantation in the stroke-injured brain.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019. Vol. 10, article id 630
Keywords [en]
neural networks, neuroengineering, cell reprogramming, disease modeling, multielectrode arrays, computational modeling, electrophysiology, cell therapy
National Category
Neurology Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-161446DOI: 10.3389/fneur.2019.00630ISI: 000471257600001OAI: oai:DiVA.org:umu-161446DiVA, id: diva2:1336749
Available from: 2019-07-10 Created: 2019-07-10 Last updated: 2019-07-10Bibliographically approved

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