人退变椎间盘髓核细胞抑制软骨终板干细胞迁移及机制的研究

It is the first time for us to demonstrate the presence of stem cells in the human degenerated intervertebral disk cartilage endplate，which named CESCs（stem cells derived from the cartilage endplate）.However, the biological function role of the CESCs in the cartilage endplate and intervertebral disc and self-repairment remains unknown. The latest study of cell migration has demonstrated that CESCs is of migration behaviour ,and the nucleus pulposus (NP) could inhibite the migration of CESCs. What is more, the ISO-1, the specific inhibitor of MIF （macrophage migration inhibitory factor）could remove the inhibition effect. Thus we hypothesis CESCs is of homing to the degenerative NP and play a repair effect,and the migration towards NP is modulated by the MIF which is secreted by NP. Based on the previous study, we need to further confirm the migration behaviour of CESCs both in vivo and in vitro. Also, the relation between migration behaviour of CESCs and MIF needs to be demonstrated. This may clarify the mechanism of the degenerative disc disease (DDD) and self-repairment. This study is of great role to help improve our understanding of intervertebral disc (IVD) pathophysiology and the degeneration process, and also the prevention and therapies of DDD in another view of point.

课题组证实人退变椎间盘软骨终板存在具有多向分化潜能的干细胞，并命名为人退变软骨终板干细胞（CESCs）。但是，CESCs在软骨终板和整个椎间盘退变及自身修复中的生物学功能还不明确。前期细胞迁移实验发现CESCs具有迁移行为，髓核细胞能够抑制CESCs的迁移，且巨噬细胞迁移抑制因子(MIF）特异性抑制剂ISO-1能够解除上述迁移抑制作用。因此，我们推测CESCs具有干细胞归巢功能向退变髓核组织中迁移并发挥修复作用，且此迁移行为被髓核细胞分泌的MIF调节。本课题拟在前期工作的基础上，通过体内、外实验，进一步证实CESCs迁移的生物学行为以及MIF抑制CESCs迁移的可能机制。从另一角度阐明椎间盘退变及自身修复的机制，为椎间盘退变性疾病的预防和治疗提供新的思路。

本课题已按计划完成了课题研究，并且取得了良好的预期效果。在实验过程中，我们完成了对人退变椎间盘临床标本的收集及原代培养与扩增；体、内外实验证实了CESCs具有迁移到髓核组织的特点；并且明确了这种迁移与MIF的调控有密切关系，迁移的CESCs数目与MIF呈浓度依赖性；体外实验明确MIF 抑制CESCs 迁移的机制；体内实验明确MIF 通过CD74 发挥抑制迁移的机制，为髓核中干细胞的来源及明确椎间盘退变性疾病的机制奠定了基础。从另一角度阐明椎间盘退变及自身修复的机制，为椎间盘退变性疾病的预防和治疗提供新的思路。