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Published August 22, 2017 | Version v1
Journal article Open

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.

  • 1. Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK.
  • 2. nstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.
  • 3. Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK; nstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile and Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile.
  • 4. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Institute for Tendon and Bone Regeneration, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria and Austrian Cluster for Tissue Regeneration, Vienna, Austria.
  • 5. Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK and Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Ophthalmology, Department of Surgery, University of Melbourne, Australia.
  • 6. nstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria and Ophthalmology/Optometry and Research Program for Experimental Ophthalmology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.
  • 7. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria and Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.
  • 8. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
  • 9. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
  • 10. Division of Neurosurgery, Zu€rich University Hospital, Zu€rich University, 8091 Zu€rich, Switzerland.
  • 11. Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile and Centro de Investigacio ́ n Biome ́ dica (CIB), Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
  • 12. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden and Integrated Cardio Metabolic Center (ICMC), Karolinska Institutet Novum, 141 57 Huddinge, Sweden.
  • 13. nstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria and Austrian Cluster for Tissue Regeneration, Vienna, Austria.
  • 14. Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK; nstitute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria; Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile and Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile.

Description

Abstract

The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

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Additional details

Funding

INMIND – Imaging of Neuroinflammation in Neurodegenerative Diseases 278850
European Commission