In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation

Abstract Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spin...

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Main Authors: Yuji Tanimoto, Tomoteru Yamasaki, Narihito Nagoshi, Yuichiro Nishiyama, Satoshi Nori, Soraya Nishimura, Tsuyoshi Iida, Masahiro Ozaki, Osahiko Tsuji, Bin Ji, Ichio Aoki, Masahiro Jinzaki, Morio Matsumoto, Yasuhisa Fujibayashi, Ming‐Rong Zhang, Masaya Nakamura, Hideyuki Okano
Format: Article
Language:English
Published: Oxford University Press 2020-04-01
Series:Stem Cells Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/sctm.19-0150
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author Yuji Tanimoto
Tomoteru Yamasaki
Narihito Nagoshi
Yuichiro Nishiyama
Satoshi Nori
Soraya Nishimura
Tsuyoshi Iida
Masahiro Ozaki
Osahiko Tsuji
Bin Ji
Ichio Aoki
Masahiro Jinzaki
Morio Matsumoto
Yasuhisa Fujibayashi
Ming‐Rong Zhang
Masaya Nakamura
Hideyuki Okano
author_facet Yuji Tanimoto
Tomoteru Yamasaki
Narihito Nagoshi
Yuichiro Nishiyama
Satoshi Nori
Soraya Nishimura
Tsuyoshi Iida
Masahiro Ozaki
Osahiko Tsuji
Bin Ji
Ichio Aoki
Masahiro Jinzaki
Morio Matsumoto
Yasuhisa Fujibayashi
Ming‐Rong Zhang
Masaya Nakamura
Hideyuki Okano
author_sort Yuji Tanimoto
collection DOAJ
description Abstract Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.
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spelling doaj.art-beada9b3135c4716ab2884e27ba886522022-12-21T20:03:45ZengOxford University PressStem Cells Translational Medicine2157-65642157-65802020-04-019446547710.1002/sctm.19-0150In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantationYuji Tanimoto0Tomoteru Yamasaki1Narihito Nagoshi2Yuichiro Nishiyama3Satoshi Nori4Soraya Nishimura5Tsuyoshi Iida6Masahiro Ozaki7Osahiko Tsuji8Bin Ji9Ichio Aoki10Masahiro Jinzaki11Morio Matsumoto12Yasuhisa Fujibayashi13Ming‐Rong Zhang14Masaya Nakamura15Hideyuki Okano16Department of Physiology Keio University School of Medicine Tokyo JapanDepartment of Advanced Nuclear Medicine Sciences National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology (QST) Chiba JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Functional Brain Imaging National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology (QST) Chiba JapanInstitute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST) Chiba JapanDepartment of Radiology Keio University School of Medicine Tokyo JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Advanced Nuclear Medicine Sciences National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology (QST) Chiba JapanDepartment of Advanced Nuclear Medicine Sciences National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology (QST) Chiba JapanDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo JapanDepartment of Physiology Keio University School of Medicine Tokyo JapanAbstract Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.https://doi.org/10.1002/sctm.19-0150human‐induced pluripotent stem cell‐derived neural stem/progenitor cellsin vivo imagingPETstem cell transplantationspinal cord injury
spellingShingle Yuji Tanimoto
Tomoteru Yamasaki
Narihito Nagoshi
Yuichiro Nishiyama
Satoshi Nori
Soraya Nishimura
Tsuyoshi Iida
Masahiro Ozaki
Osahiko Tsuji
Bin Ji
Ichio Aoki
Masahiro Jinzaki
Morio Matsumoto
Yasuhisa Fujibayashi
Ming‐Rong Zhang
Masaya Nakamura
Hideyuki Okano
In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation
Stem Cells Translational Medicine
human‐induced pluripotent stem cell‐derived neural stem/progenitor cells
in vivo imaging
PET
stem cell transplantation
spinal cord injury
title In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation
title_full In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation
title_fullStr In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation
title_full_unstemmed In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation
title_short In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell‐derived neural stem/progenitor cells transplantation
title_sort in vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell derived neural stem progenitor cells transplantation
topic human‐induced pluripotent stem cell‐derived neural stem/progenitor cells
in vivo imaging
PET
stem cell transplantation
spinal cord injury
url https://doi.org/10.1002/sctm.19-0150
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