内源性修复失效是椎间盘退行性变的主要原因。国外及我们最新研究提示，椎间盘干细胞在椎间盘内源性修复中发挥重要作用。如何在椎间盘内压力低氧等不利微环境下维持数量足够、活性良好的干细胞是亟待解决的关键问题。.本项目拟在长期从事椎间盘退行性变机制和修复再生研究的基础上，以椎间盘干细胞为切入点，利用前期发明的椎间盘在体可控轴向加压模型和可控气压加压细胞培养装置，深入研究盘内压力低氧微环境对椎间盘干细胞迁移、归巢、死亡等生物学行为的影响；探讨椎间盘干细胞自噬、凋亡、坏死性凋亡的相互关系及串扰影响，阐明椎间盘退行性变过程中内源性修复失效的分子机制，从复杂网络中发现关键调控靶点；同时针对性设计一种携带多重生物信号的自组装多肽纳米纤维凝胶材料，多方位、协同、序贯诱导椎间盘干细胞向盘内迁移、归巢及定向分化，提高其质和量，从而促进髓核原位再生。.本项目将丰富椎间盘退行性变及修复的理论，为其生物学治疗提供全新策略

The failure of endogenous repair is the main cause of intervertebral disc (IVD) degeneration. Both foreign and our latest studies suggest that IVD stem cells play an essential role in IVD endogenous repair. However, it’s the key issue that how to maintain the sufficiency and vitality of stem cells under the adverse microenvironment comprising pressure and hypoxia..The study is based on our long-term researches on the mechanism and regeneration of IVD degeneration. Taking the IVD stem cells as the breakthrough point, with the help of the self-designed controllable axial loading induced IVD degeneration model in vivo and the self-designed controllable air-pressure cell culture apparatus in vitro, we will make further studies on the influence of adverse microenviroment on the biological behavior of IVD stem cells, such as migration, homing and death, as well as discuss the relationship and crosstalk of autophagy, apoptosis and necrosis of IVD stem cells, so as to clarify the molecular mechanism of fail of endogenous repair during IVD degeneration and to find the key regulatory target from the complicated network. Following that, we will pertinently design self-assembling peptide nanofiber scaffolds with multiple bio-signals in order to induce the migration, homing and differentiation of stem cells, contributing to the in situ regeneration of nucleus pulposus..The study will enrich the theories of degeneration and regeneration of IVD. It will provide a new strategy of biological therapy for IVD degeneration.