Connexin激活的CXCL12/CXCR4通路在力学诱导的大体积工程化脂肪瓣构建中的机制研究

以乳房再造为代表的大体积软组织缺损修复是整形外科面临的最大挑战，经典治疗难以摆脱“拆东墙补西墙”。再生诱导为软组织缺损后再生提供了可能。本课题组前期改进了经典的组织工程技术，通过独特的体外力学诱导实现了全内源性大体积脂肪新生，并初步揭示了CXCL12/CXCR4通路趋化脂肪前体细胞参与再生。进一步研究发现机械力解除细胞间接触继而上调Connexin表达，才是激活该通路的核心。由此我们采用微球囊扩张解除脂肪组织接触，上调Connexin启动下游趋化因子通路。该方案仅依靠体组织内微创分离即可实现原位大体积脂肪新生。本研究将紧紧围绕这个发现，拟采用基因敲除、可控力学细胞培养、转基因荧光动物细胞示踪等方法，重点研究机械力介导Connexin上调的具体分子机制以及CD34+脂肪前体细胞受趋化后的迁移模式而展开，探索力学在脂肪原位再生中的具体机制，为临床修复大体积软组织缺损提供理论依据及实验数据

Repair of large volume soft tissue defect, especially breast reconstruction is the biggest challenge for plastic surgeons, for donor site morbidity is inevitable with surgery. Tissue regeneration offers a new solution to the reconstructive surgery. Based on the studies of traditional tissue engineering technique, our research group first developed this novel adipose regeneration procedure to generate endogenous large-volume adipose flap. This process was initiated by adipose precursor cell through CXCL12/CXCR4 pathway. Further result suggested that Connexin expression triggered by mechanical force played an important role during this model. Thus, a micro tissue expender was used to reduce tissue connection to regenerating large volume adipose tissue. The following researches will focus on the inhibition of Connexin by mechanical force using cytobiology, microarray analysis, bone marrow transplantation and histomorphology methods, clarifying the role that mechanical-biochemical signal plays in the adipose regeneration process. This research is believed to be helpful for better understanding the regeneration process of adipose tissue.