Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus

Direct conversion of human somatic cells to induced neurons (iNs), using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where...

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Main Authors: Natalia Avaliani, Ulrich Pfisterer, Andreas Heuer, Malin Parmar, Merab Kokaia, My Andersson
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/5718608
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author Natalia Avaliani
Ulrich Pfisterer
Andreas Heuer
Malin Parmar
Merab Kokaia
My Andersson
author_facet Natalia Avaliani
Ulrich Pfisterer
Andreas Heuer
Malin Parmar
Merab Kokaia
My Andersson
author_sort Natalia Avaliani
collection DOAJ
description Direct conversion of human somatic cells to induced neurons (iNs), using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where populations of inhibitory interneurons degenerate. Thus, iNs could be of potential use to replace these lost interneurons. It is not known, however, if iNs survive and maintain functional neuronal properties for prolonged time periods in in vivo. We transplanted human fibroblast-derived iNs into the adult rat hippocampus and observed a progressive morphological differentiation, with more developed dendritic arborisation at six months as compared to one month. This was accompanied by mature electrophysiological properties and fast high amplitude action potentials at six months after transplantation. This proof-of-principle study suggests that human iNs can be developed as a candidate source for cell replacement therapy in temporal lobe epilepsy.
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institution Kabale University
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spelling doaj-art-23404c6948804e0089cbbc60f812eb652025-02-03T01:22:19ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/57186085718608Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent HippocampusNatalia Avaliani0Ulrich Pfisterer1Andreas Heuer2Malin Parmar3Merab Kokaia4My Andersson5Epilepsy Centre, Lund University Hospital, Lund, SwedenDevelopmental Neurobiology, Lund University, Lund, SwedenDevelopmental Neurobiology, Lund University, Lund, SwedenDevelopmental Neurobiology, Lund University, Lund, SwedenEpilepsy Centre, Lund University Hospital, Lund, SwedenEpilepsy Centre, Lund University Hospital, Lund, SwedenDirect conversion of human somatic cells to induced neurons (iNs), using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where populations of inhibitory interneurons degenerate. Thus, iNs could be of potential use to replace these lost interneurons. It is not known, however, if iNs survive and maintain functional neuronal properties for prolonged time periods in in vivo. We transplanted human fibroblast-derived iNs into the adult rat hippocampus and observed a progressive morphological differentiation, with more developed dendritic arborisation at six months as compared to one month. This was accompanied by mature electrophysiological properties and fast high amplitude action potentials at six months after transplantation. This proof-of-principle study suggests that human iNs can be developed as a candidate source for cell replacement therapy in temporal lobe epilepsy.http://dx.doi.org/10.1155/2017/5718608
spellingShingle Natalia Avaliani
Ulrich Pfisterer
Andreas Heuer
Malin Parmar
Merab Kokaia
My Andersson
Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
Stem Cells International
title Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
title_full Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
title_fullStr Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
title_full_unstemmed Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
title_short Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
title_sort directly converted human fibroblasts mature to neurons and show long term survival in adult rodent hippocampus
url http://dx.doi.org/10.1155/2017/5718608
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