Published March 24, 2015 | Version v1
Journal article Open

Lesion-induced accumulation of platelets promotes survival of adult neural stem / progenitor cells.

  • 1. Wellcome Trust and MRC Cambridge Stem Cell Institute & Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom and Department of Biology, University of Patras, Patras, Greece.
  • 2. Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University and Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 3. Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria and Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria
  • 4. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Austria and Institute of Tendon and Bone Regeneration, Paracelsus Medical University Salzburg, Austria and Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 5. Division of Molecular Dermatology and EB House Austria, Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 6. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Austria and Department of Blood Group Serology and Transfusion Medicine, Federal Hospital of Salzburg and Paracelsus Medical University, Salzburg, Austria and Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 7. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University and Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 8. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University and Ophthalmology/Optometry and Research Program for Experimental Ophthalmology, Paracelsus Medical University, Salzburg, Austria
  • 9. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University and Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 10. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University and Institute of Tendon and Bone Regeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • 11. Wellcome Trust and MRC Cambridge Stem Cell Institute & Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
  • 12. Wellcome Trust and MRC Cambridge Stem Cell Institute & Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom, Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria and Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University

Description

The presence of neural stem/progenitor cells (NSPCs) in specific areas of the central nervous system (CNS) supports tissue maintenance as well as regeneration. The subependymal zone (SEZ), located at the lateral ventricle’s wall, represents a niche for NSPCs and in response to stroke or demyelination becomes activated with progenitors migrating towards the lesion and differentiating into neurons and glia. The mechanisms that underlie this phenomenon remain largely unknown. The vascular niche and in particular blood-derived elements such as platelets, has been shown to contribute to CNS regeneration in different pathological conditions. Indeed, intracerebroventricularly administrated platelet lysate (PL) stimulates angiogenesis, neurogenesis and neuroprotection in the damaged CNS. Here, we explored the presence of platelets in the activated SEZ after a focal demyelinating lesion in the corpus callosum of mice and we studied the effects of PL on proliferating SEZ-derived NSPCs in vitro. We showed that the lesion induced increase in the size of the SEZ and in the number of proliferating SEZ-resident NSPCs correlates with the accumulation of platelets specifically along the activated SEZ vasculature. Expanding on this finding, we demonstrated that exposure of NSPCs to PL in vitro led to increased numbers of cells by enhanced cell survival and reduced apoptosis without differences in proliferation and in the differentiation potential of NSPCs. Finally, we demonstrate that the accumulation of platelets within the SEZ is spatially correlated with reduced numbers of apoptotic cells when compared to other periventricular areas. In conclusion, our results show that platelet-derived compounds specifically promote SEZ-derived NSPC survival and suggest that platelets might contribute to the enlargement of the pool of SEZ NSPCs that are available for CNS repair in response to injury.

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Funding

INMIND – Imaging of Neuroinflammation in Neurodegenerative Diseases 278850
European Commission