SDF-1/CXCR4信号通路参与BMP-2诱导MSCs归巢效应的机制研究

The bottleneck of clinical transformation of tissue engineered bone is to seek appropriate seeding cells. There are many issues of autogeneic source of seeding cells,such as quantity insufficient,collection inconvenient. Allogeneic source of seeding cells have immunogenic,subject to ethical constraints and long-term efficacy indefinite. Our previous research has confirmed that new type tissue engineered bone (rhBMP-2/allogeneic bone) has good osteogenic effect,also found its ability of recruiting cells in early stage (homing effect),but the homing mechanism is still not clear. Studies have shown that the SDF-1/CXCR4 signaling pathway play a key role in stem cell recruitment during the process of tissue repair,suggesting that the SDF-1/CXCR4 signaling pathway may be also very important in BMP-2 induced cells homing process.Our group intends to study in vitro(co-culture) and in vivo(labeling technique),through a variety of research methods such as micro-fluidic chip technique to explore the effect of the positive intervention (stimulation SDF-1) and reverse intervention (blocking SDF-1) in bone regernation, in order to reveal the interaction mechanism of contact between SDF-1/CXCR4 signaling pathway and BMP-2 in the process of bone regeneration. Its exploration has potential application value in seeding cells homing, to provide a theoretical basis for clinical transformation of tissue engineered bone.

骨组织工程临床转化的瓶颈是获取适宜的种子细胞。自体种子细胞数量有限、取材不便等诸多问题；异体种子细胞具有免疫原性，受到伦理限制且长远疗效不确切。本课题组前期证实组织工程骨（rhBMP-2/异体骨）具有良好成骨效应，同时具有早期募集种子细胞能力（归巢效应），但其机制不明确。研究显示SDF-1/CXCR4信号通路在诱导干细胞归巢修复组织损伤过程中发挥关键作用，因此推测SDF-1/CXCR4信号通路可能在BMP-2诱导种子细胞归巢过程中发挥作用。本课题拟从体外实验（共培养）和体内实验（活体细胞标记示踪）两个层面，采用微流控芯片技术等多种研究方法探讨正向干预（SDF-1刺激）和反向干预（SDF-1阻断）对种子细胞归巢效应的影响，以期揭示SDF-1/CXCR4信号通路与BMP-2之间联系及在骨修复过程中的作用机制,探索该信号通路在诱导种子细胞归巢中的潜在价值，为组织工程骨临床转化应用提供理论依据。

骨组织工程临床转化的瓶颈是获取适宜的种子细胞。自体种子细胞数量有限、取材不便等诸多问题；异体种子细胞具有免疫原性，受到伦理限制且长远疗效不确切。本课题组前期证实组织工程骨（rhBMP-2/异体骨）具有良好成骨效应，同时具有早期募集种子细胞能力，研究显示SDF-1/CXCR4信号通路在诱导干细胞归巢修复组织损伤过程中发挥关键作用，因此推测SDF-1/CXCR4信号通路可能在BMP-2诱导种子细胞归巢过程中发挥作用。本课题组对SD大鼠间充质干细胞在BMP-2作用下正反通路信号干预对细胞迁移、成骨分化的影响；并对联合BMP-2双生物因子体外成骨效应进行了研究；开展了BMP-2调节间充质干细胞早期体内成活关键生物因子VEGF表达的生物学规律及其机制进行了研究，对干细胞植入体内生物材料进行了探索；对多种干细胞复合支架材料联合植入体内活体观测成活情况进行了研究。探索该信号通路在BMP-2作用下在诱导种子细胞归巢及成骨效应，为组织工程骨临床转化应用提供理论依据。