Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke
Stem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factor...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/4061516 |
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| author | Seung-Hun Oh Yong-Woo Jeong Wankyu Choi Jeong-Eun Noh Suji Lee Hyun-Sook Kim Jihwan Song |
| author_facet | Seung-Hun Oh Yong-Woo Jeong Wankyu Choi Jeong-Eun Noh Suji Lee Hyun-Sook Kim Jihwan Song |
| author_sort | Seung-Hun Oh |
| collection | DOAJ |
| description | Stem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factors can induce nonviral, integration-free iPSCs. Thus, iPSCs generated by an EP-based reprogramming technique (ep-iPSCs) have an advantage over gene-integrating iPSCs for clinical applications. However, there are few studies regarding the in vivo efficacy of ep-iPSCs. In this study, we investigated the therapeutic potential of intracerebral transplantation of neural precursor cells differentiated from ep-iPSCs (ep-iPSC-NPCs) in a rodent stroke model. The ep-iPSC-NPCs were transplanted intracerebrally in a peri-infarct area in a rodent stroke model. Rats transplanted with fibroblasts and vehicle were used as controls. The ep-iPSC-NPC-transplanted animals exhibited functional improvements in behavioral and electrophysiological tests. A small proportion of ep-iPSC-NPCs were detected up to 12 weeks after transplantation and were differentiated into both neuronal and glial lineages. In addition, transplanted cells promoted endogenous brain repair, presumably via increased subventricular zone neurogenesis, and reduced poststroke inflammation and glial scar formation. Taken together, these results strongly suggest that intracerebral transplantation of ep-iPSC-NPCs is a useful therapeutic option to treat clinical stroke through multimodal therapeutic mechanisms. |
| format | Article |
| id | doaj-art-d2f57ddc311f4b1a8b6e92ec767244eb |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-d2f57ddc311f4b1a8b6e92ec767244eb2025-08-20T02:19:50ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/40615164061516Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic StrokeSeung-Hun Oh0Yong-Woo Jeong1Wankyu Choi2Jeong-Eun Noh3Suji Lee4Hyun-Sook Kim5Jihwan Song6Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaCHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaCHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaCHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaCHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaDepartment of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaCHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam, Gyeonggi-do, Republic of KoreaStem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factors can induce nonviral, integration-free iPSCs. Thus, iPSCs generated by an EP-based reprogramming technique (ep-iPSCs) have an advantage over gene-integrating iPSCs for clinical applications. However, there are few studies regarding the in vivo efficacy of ep-iPSCs. In this study, we investigated the therapeutic potential of intracerebral transplantation of neural precursor cells differentiated from ep-iPSCs (ep-iPSC-NPCs) in a rodent stroke model. The ep-iPSC-NPCs were transplanted intracerebrally in a peri-infarct area in a rodent stroke model. Rats transplanted with fibroblasts and vehicle were used as controls. The ep-iPSC-NPC-transplanted animals exhibited functional improvements in behavioral and electrophysiological tests. A small proportion of ep-iPSC-NPCs were detected up to 12 weeks after transplantation and were differentiated into both neuronal and glial lineages. In addition, transplanted cells promoted endogenous brain repair, presumably via increased subventricular zone neurogenesis, and reduced poststroke inflammation and glial scar formation. Taken together, these results strongly suggest that intracerebral transplantation of ep-iPSC-NPCs is a useful therapeutic option to treat clinical stroke through multimodal therapeutic mechanisms.http://dx.doi.org/10.1155/2020/4061516 |
| spellingShingle | Seung-Hun Oh Yong-Woo Jeong Wankyu Choi Jeong-Eun Noh Suji Lee Hyun-Sook Kim Jihwan Song Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke Stem Cells International |
| title | Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke |
| title_full | Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke |
| title_fullStr | Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke |
| title_full_unstemmed | Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke |
| title_short | Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke |
| title_sort | multimodal therapeutic effects of neural precursor cells derived from human induced pluripotent stem cells through episomal plasmid based reprogramming in a rodent model of ischemic stroke |
| url | http://dx.doi.org/10.1155/2020/4061516 |
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