Oligodendrocyte precursors gain Schwann cell-like phenotype and remyelinate axons upon engraftment into peripheral nerves
Ruifa Mi
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorMarkus Tammia
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorDaniel Shinn
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorYing Li
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorRussell Martin
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorCorresponding Author
Hai-Quan Mao
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
Correspondence
Hai-Quan Mao, Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Email: [email protected]
Ahmet Höke, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Ahmet Höke
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Correspondence
Hai-Quan Mao, Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Email: [email protected]
Ahmet Höke, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Email: [email protected]
Search for more papers by this authorRuifa Mi
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorMarkus Tammia
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorDaniel Shinn
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorYing Li
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorRussell Martin
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorCorresponding Author
Hai-Quan Mao
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
Correspondence
Hai-Quan Mao, Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Email: [email protected]
Ahmet Höke, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Ahmet Höke
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Correspondence
Hai-Quan Mao, Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Email: [email protected]
Ahmet Höke, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Email: [email protected]
Search for more papers by this authorAbstract
The ability to treat large peripheral nerve injuries may be greatly advanced if an accessible source of human myelinating cells is identified, as it overcomes one of the major limitations of acellular or synthetic nerve guides compared with autografts, the gold standard for large defect repair. Methods to derive oligodendrocyte precursor cells (OPCs) from human pluripotent stem cells have advanced to the point where they have been shown capable of myelination and are being evaluated in clinical trials. Here, we test the hypothesis that OPCs can survive and remyelinate axons in the peripheral nervous system during a repair process. Using freshly isolated OPCs from mouse post-natal brains, we engrafted these OPCs into the tibial nerve immediately after it being subjected to cryolesioning. At 1-month postengraftment, we found numerous graft-derived cells that survived in this environment, and many transplanted cells expressed Schwann cell markers such as periaxin and S100β coexpressed with myelin basic protein, whereas oligodendrocyte markers O4 and Olig2 were virtually absent. Our results demonstrate that OPCs can survive in a peripheral nervous system micro-environment and undergo niche-dependent transdifferentiation into Schwann cell-like cells as has previously been observed in central nervous system focal demyelination models, suggesting that OPCs constitute an accessible source of cells for peripheral nerve cell therapies.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| term2935-sup-0001-F1.docxWord 2007 document , 1.8 MB |
Figure S1. Expression of oligodendrocyte precursor cell markers were confirmed in isolated cells from P4-P5 mouse brains. (A-B) O4 staining and cell membrane localization was confirmed in the isolated cells, present in 81.4% ±10.2% of the cells. (C-D) 67.2% ±14.6% of the cells also expressed the cell-surface marker A2B5, and (E-F) 87.5% ±6.1% was positive for the transcription factor Olig-2. Inserts in A-D show orthogonal projections of images at higher magnification. GFP expression is under a CAG promoter. Scale bars = 100 μm. Quantifications were made on n = 4 batches of cell isolations, and presented as mean ± standard deviation. Figure S2. Positive controls for oligodendrocyte lineage marker stains. (A) Staining for myelinating oligodendrocyte glycoprotein (MOG) in adult mouse corpus callosum. (B-C) Olig2 staining in adult Plp-eGFP mouse cortex. Arrows indicate examples of co-localization of Plp-eGFP+ (green) oligodendrocytes with nuclear expression of Olig2 (red). Scale bar in A = 20 μm, and in B-C 50 μm. Table S1. Antibodies used for immunocytochemistry and immunohistochemistry |
| term2935-sup-0002-F1.docxWord 2007 document , 246.1 KB | Data S1. Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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