Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke

Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) is a major type of stroke, but there are currently very limited therapeutic options for its cure. Neural stem cells (NSCs) or neural precursor cells (NPCs) derived from various sources are known to survive and improve neurologi...

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Main Authors: Da-Jeong Chang, Nayeon Lee, In-Hyun Park, Chunggab Choi, Iksoo Jeon, Jihye Kwon, Seung-Hun Oh, Dong Ah Shin, Jeong Tae Do, Dong Ryul Lee, Hyunseung Lee, Kwan Soo Hong, George Q. Daley, Jihwan Song D.Phil., Hyeyoung Moon
Format: Article
Language:English
Published: SAGE Publishing 2013-08-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368912X657314
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author Da-Jeong Chang
Nayeon Lee
In-Hyun Park
Chunggab Choi
Iksoo Jeon
Jihye Kwon
Seung-Hun Oh
Dong Ah Shin
Jeong Tae Do
Dong Ryul Lee
Hyunseung Lee
Kwan Soo Hong
George Q. Daley
Jihwan Song D.Phil.
Hyeyoung Moon
author_facet Da-Jeong Chang
Nayeon Lee
In-Hyun Park
Chunggab Choi
Iksoo Jeon
Jihye Kwon
Seung-Hun Oh
Dong Ah Shin
Jeong Tae Do
Dong Ryul Lee
Hyunseung Lee
Kwan Soo Hong
George Q. Daley
Jihwan Song D.Phil.
Hyeyoung Moon
author_sort Da-Jeong Chang
collection DOAJ
description Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) is a major type of stroke, but there are currently very limited therapeutic options for its cure. Neural stem cells (NSCs) or neural precursor cells (NPCs) derived from various sources are known to survive and improve neurological functions when they are engrafted in animal models of stroke. Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients are novel cells that promise the autologous cell therapy for stroke. In this study, we successfully differentiated iPSCs derived from human fibroblasts into NPCs and found their robust therapeutic potential in a rodent MCAo stroke model. We observed the significant graft-induced behavioral recovery, as well as extensive neural tissue formation. Animal MRI results indicated that the majority of contralaterally transplanted iPSC-derived NPCs migrated to the peri-infarct area, showing a pathotropism critical for tissue recovery. The transplanted animals exhibited the significant reduction of stroke-induced inflammatory response, gliosis and apoptosis, and the contribution to the endogenous neurogenesis. Our results demonstrate that iPSC-derived NPCs are effective cells for the treatment of stroke.
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spelling doaj.art-d42b33b8a8704cc79919cd2b53c5bd442022-12-21T23:57:42ZengSAGE PublishingCell Transplantation0963-68971555-38922013-08-012210.3727/096368912X657314Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental StrokeDa-Jeong Chang0Nayeon Lee1In-Hyun Park2Chunggab Choi3Iksoo Jeon4Jihye Kwon5Seung-Hun Oh6Dong Ah Shin7Jeong Tae Do8Dong Ryul Lee9Hyunseung Lee10Kwan Soo Hong11George Q. Daley12Jihwan Song D.Phil.13Hyeyoung Moon14 CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea Department of Genetics, Yale University School of Medicine, New Haven, CT, USA CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Korea Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Korea Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, KoreaIschemic stroke mainly caused by middle cerebral artery occlusion (MCAo) is a major type of stroke, but there are currently very limited therapeutic options for its cure. Neural stem cells (NSCs) or neural precursor cells (NPCs) derived from various sources are known to survive and improve neurological functions when they are engrafted in animal models of stroke. Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients are novel cells that promise the autologous cell therapy for stroke. In this study, we successfully differentiated iPSCs derived from human fibroblasts into NPCs and found their robust therapeutic potential in a rodent MCAo stroke model. We observed the significant graft-induced behavioral recovery, as well as extensive neural tissue formation. Animal MRI results indicated that the majority of contralaterally transplanted iPSC-derived NPCs migrated to the peri-infarct area, showing a pathotropism critical for tissue recovery. The transplanted animals exhibited the significant reduction of stroke-induced inflammatory response, gliosis and apoptosis, and the contribution to the endogenous neurogenesis. Our results demonstrate that iPSC-derived NPCs are effective cells for the treatment of stroke.https://doi.org/10.3727/096368912X657314
spellingShingle Da-Jeong Chang
Nayeon Lee
In-Hyun Park
Chunggab Choi
Iksoo Jeon
Jihye Kwon
Seung-Hun Oh
Dong Ah Shin
Jeong Tae Do
Dong Ryul Lee
Hyunseung Lee
Kwan Soo Hong
George Q. Daley
Jihwan Song D.Phil.
Hyeyoung Moon
Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
Cell Transplantation
title Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
title_full Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
title_fullStr Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
title_full_unstemmed Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
title_short Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
title_sort therapeutic potential of human induced pluripotent stem cells in experimental stroke
url https://doi.org/10.3727/096368912X657314
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