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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2017-01-01
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Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2017/5718608 |
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doaj-23404c6948804e0089cbbc60f812eb652020-11-25T00:18:30ZengHindawi LimitedStem 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 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natalia Avaliani Ulrich Pfisterer Andreas Heuer Malin Parmar Merab Kokaia My Andersson |
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 |
author_facet |
Natalia Avaliani Ulrich Pfisterer Andreas Heuer Malin Parmar Merab Kokaia My Andersson |
author_sort |
Natalia Avaliani |
title |
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_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_sort |
directly converted human fibroblasts mature to neurons and show long-term survival in adult rodent hippocampus |
publisher |
Hindawi Limited |
series |
Stem Cells International |
issn |
1687-966X 1687-9678 |
publishDate |
2017-01-01 |
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. |
url |
http://dx.doi.org/10.1155/2017/5718608 |
work_keys_str_mv |
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