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.
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.
Exp Neurol. 2015 Jul;269:75-89. doi: 10.1016/j.expneurol.2015.03.018. Epub 2015 Mar 24.
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.
神经干细胞/祖细胞（NSPCs）存在于中枢神经系统（CNS）的特定区域，支持组织维持和再生。室管膜下区（SEZ）位于侧脑室壁，是 NSPC 的龛位，在中风或脱髓鞘后，祖细胞向病变部位迁移并分化为神经元和神经胶质细胞，SEZ 被激活。这种现象的机制在很大程度上仍然未知。血管龛位，特别是血小板等血液来源的成分，已被证明在不同的病理条件下有助于 CNS 再生。事实上，脑室内给予血小板裂解液（PL）可刺激损伤的 CNS 中的血管生成、神经发生和神经保护。在这里，我们研究了在小鼠胼胝体局灶性脱髓鞘病变后激活的 SEZ 中血小板的存在，并研究了 PL 对体外增殖 SEZ 源性 NSPC 的影响。我们发现，SEZ 大小的增加和增殖的 SEZ 驻留 NSPC 数量的增加与血小板的积累有关，特别是沿着激活的 SEZ 血管。在此基础上，我们证明了 NSPC 暴露于 PL 可通过增强细胞存活和减少细胞凋亡来增加细胞数量，而对 NSPC 的增殖和分化潜能没有影响。最后，我们证明与其他脑室周围区域相比，SEZ 内血小板的积累与凋亡细胞数量的减少呈空间相关。总之，我们的结果表明，血小板衍生的化合物特异性地促进 SEZ 源性 NSPC 的存活，并表明血小板可能有助于扩大 SEZ NSPC 池，以应对损伤进行 CNS 修复。
