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

作者信息

Tanimoto Yuji, Yamasaki Tomoteru, Nagoshi Narihito, Nishiyama Yuichiro, Nori Satoshi, Nishimura Soraya, Iida Tsuyoshi, Ozaki Masahiro, Tsuji Osahiko, Ji Bin, Aoki Ichio, Jinzaki Masahiro, Matsumoto Morio, Fujibayashi Yasuhisa, Zhang Ming-Rong, Nakamura Masaya, Okano Hideyuki

机构信息

Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.

出版信息

Stem Cells Transl Med. 2020 Apr;9(4):465-477. doi: 10.1002/sctm.19-0150. Epub 2020 Jan 6.


DOI:10.1002/sctm.19-0150
PMID:31904914
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7103627/
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 [ F] 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 [ F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/3d8377e84915/SCT3-9-465-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/1aa05ff0cf6b/SCT3-9-465-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/67f78836db3e/SCT3-9-465-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/f33e5c33ffe8/SCT3-9-465-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/1f40bc1b776f/SCT3-9-465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/3b9122a91b91/SCT3-9-465-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/3d8377e84915/SCT3-9-465-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/1aa05ff0cf6b/SCT3-9-465-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/67f78836db3e/SCT3-9-465-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/f33e5c33ffe8/SCT3-9-465-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/1f40bc1b776f/SCT3-9-465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/3b9122a91b91/SCT3-9-465-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5679/7103627/3d8377e84915/SCT3-9-465-g006.jpg

相似文献

[1]
In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation.

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[7]
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引用本文的文献

[1]
Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury.

Neural Regen Res. 2025-11-1

[2]
Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers.

Sci Rep. 2023-9-30

[3]
Effect of Electroacupuncture Stimulation on Proliferation and Differentiation of Endogenous Neural Stem Cells in Rats with Spinal Cord Injury.

Mol Neurobiol. 2024-2

[4]
Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.

World J Stem Cells. 2023-7-26

[5]
A Narrative Review of Advances in Neural Precursor Cell Transplantation Therapies for Spinal Cord Injury.

Neurospine. 2022-12

[6]
Morphological Characterization of Astrocytes in a Xenograft of Human iPSCDerived Neural Precursor Cells.

Acta Naturae. 2022

[7]
Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Promotes Forelimb Functional Recovery after Cervical Spinal Cord Injury.

Cells. 2022-9-5

[8]
Tracking Neural Stem Cells in vivo: Achievements and Limitations.

Stem Cell Rev Rep. 2022-6

[9]
Modulation by DREADD reveals the therapeutic effect of human iPSC-derived neuronal activity on functional recovery after spinal cord injury.

Stem Cell Reports. 2022-1-11

[10]
A Hyaluronic Acid Demilune Scaffold and Polypyrrole-Coated Fibers Carrying Embedded Human Neural Precursor Cells and Curcumin for Surface Capping of Spinal Cord Injuries.

Biomedicines. 2021-12-16

本文引用的文献

[1]
LOTUS Inhibits Neuronal Apoptosis and Promotes Tract Regeneration in Contusive Spinal Cord Injury Model Mice.

eNeuro. 2018-12-14

[2]
Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury.

Stem Cells Transl Med. 2018-11-28

[3]
Combination of drug and stem cells neurotherapy: Potential interventions in neurotrauma and traumatic brain injury.

Neuropharmacology. 2018-9-26

[4]
A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury.

Cell Stem Cell. 2018-6-1

[5]
Intratumoral evaluation of 3D microvasculature and nanoparticle distribution using a gadolinium-dendron modified nano-liposomal contrast agent with magnetic resonance micro-imaging.

Nanomedicine. 2018-4-4

[6]
The pathophysiological role of acute inflammation after spinal cord injury.

Inflamm Regen. 2016-10-17

[7]
PET Imaging of Human Brown Adipose Tissue with the TSPO Tracer [C]PBR28.

Mol Imaging Biol. 2018-4

[8]
TSPO PET for glioma imaging using the novel ligand F-GE-180: first results in patients with glioblastoma.

Eur J Nucl Med Mol Imaging. 2017-8-19

[9]
Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives.

Stem Cell Reports. 2017-3-14

[10]
Whole-Genome DNA Methylation Analyses Revealed Epigenetic Instability in Tumorigenic Human iPS Cell-Derived Neural Stem/Progenitor Cells.

Stem Cells. 2017-2-23

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