title: Lesion-induced accumulation of platelets promotes survival of adult neural stem / progenitor cells.
abstract: 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.
authors.affiliation: Wellcome Trust and MRC Cambridge Stem Cell Institute & Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Biology, University of Patras, Patras, Greece.
authors.forename: Ilias
authors.initials: I
authors.lastname: Kazanis
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg Salzburg, Salzburg, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Feichtner
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Simona
authors.initials: S
authors.lastname: Lange
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Rotheneichner
authors.affiliation: Division of Molecular Dermatology and EB House Austria, Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hainzl
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg Salzburg, Salzburg, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Öller
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg Salzburg, Salzburg, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schallmoser
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Department of Blood Group Serology and Transfusion Medicine, Federal Hospital and Paracelsus Medical University Salzburg Salzburg, Salzburg, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Rohde
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Ophthalmology/Optometry and Research Program for Experimental Ophthalmology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Reitsamer
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Couillard-Despres
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria; Institute of Tendon and Bone Regeneration, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Bauer
authors.affiliation: Wellcome Trust and MRC Cambridge Stem Cell Institute & Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
authors.affiliation: 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; Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria. Electronic address: francisco.rivera@pmu.ac.at.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rivera
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D001930:Brain Injuries / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003711:Demyelinating Diseases / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology
keywords: CNS damage; Cell Survival; Neural Stem / Progenitor Cells; Platelets; Subependymal Zone; Subventricular Zone; Vascular Niche