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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Kuai, Xiao Ling Ni, Run Zhou Zhou, Guo Xiong Mao, Zheng Biao Zhang, Jian Feng Yi, Nan Liu, Zhao Xiu Shao, Nan Ni, Wen Kai Wang, Zhi Wei |
| Abstract | Introduction Globoid cell leukodystrophy (GLD) is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. Cell-based therapies are highly promising strategies for GLD. In this study, G-Olig2 mouse embryonic stem cells (ESCs) were induced into oligodendrocyte progenitor cells (OPCs) and were implanted into the brains of twitcher mice, an animal model of GLD, to explore the therapeutic potential of the cells. Methods The G-Olig2 ESCs were induced into OPCs by using cytokines and a multi-step differentiation procedure. Oligodendrocyte markers were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. The toxicity of psychosine to OPCs was determined by a cell proliferation assay kit. The GALC level of OPCs was also examined. OPCs were labeled with Dir and transplanted into the brains of twitcher mice. The transplanted cells were detected by in-Vivo Multispectral Imaging System and real-time PCR. The physiological effects of twitcher mice were assessed. Results Oligodendrocyte markers were expressed in OPCs, and 76% ± 5.76% of the OPCs were enhanced green fluorescent protein (eGFP)-positive, eGFP was driven by the Olig2 promoter. The effect of psychosine on cell viability indicated that OPCs were more resistant to psychosine toxicity. The GALC level of OPCs was 10.0 ± 1.23 nmol/hour per mg protein, which was significantly higher than other cells. Dir-labeled OPCs were injected into the forebrain of post-natal day 10 twitcher mice. The transplanted OPCs were myelin basic protein (MBP)-positive and remained along the injection tract as observed by fluorescent microscopy. The level of the Dir fluorescent signal and eGFP mRNA significantly decreased at days 10 and 20 after injection, as indicated by in-Vivo Multispectral Imaging System and real-time PCR. Because of poor cell survival and limited migration ability, there was no significant improvement in brain GALC activity, MBP level, life span, body weight, and behavioral deficits of twitcher mice. Conclusions ESC-derived OPC transplantation was not sufficient to reverse the clinical course of GLD in twitcher mice. |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/s13287-015-0024-2.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/s13287-015-0024-2 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 1 |
| Volume Number | 6 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2015-03-14 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Myelin Basic Protein Twitcher Mouse Globoid Cell Leukodystrophy Myelin Basic Protein Expression Nikon Eclipse E600 Fluorescence Microscope Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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