脂肪来源干细胞构建组织工程鼻软骨过程中细胞支架复合物收缩形变机制的研究和对策

Tissue engineering technology provides a new way for nasal cartilage regeneration, however, the issue of seeding cell limits its clinical application. Adipose derived stem cells (ADSC), as a group of adult stem cells featured in rich source of plastic surgery, and minimal injury of donor sites, have been proven to possess good ability of chondrogenesis and thus considered as an ideal seeding cells for clinical application. However, an obvious shrinkage and deformation of ADSC-scaffold complex was observed during in vitro chondrogenic induction, and that can not maintain the prefabricated shape of the scaffold. According to the literatures and our preliminary research, it can be speculated that the up-regulation of smooth muscle actin-alpha (SMA-α) caused by chondrogenic induction is one of the leading reason. In this study, to clarify the relationship between SMA-α and the deformation of ADSC engineered cartilage, we use overexpression and RNA interference technique with lentiviral vector to specificly up-regulate or block the expression of SMA-α. On this basis, we add SMA-α inhibition factor with collaborative chondrogenic ability to antagonize the shrinkage of ADSC-scaffold complex in vitro and further explore the feasibility of nasal cartilage engineering to provide autologous cartilage graft for clinical nasal defect repair and reconstruction.

组织工程技术是鼻软骨再生的一种全新手段，然而种子细胞问题限制了该技术的临床应用。脂肪来源干细胞（ADSC）在整形外科手术中来源丰富，取材创伤小，并具有软骨分化潜能，很适合临床推广应用。但是，ADSC-支架材料复合物在体外软骨诱导过程中很容易发生收缩形变，无法维持支架材料的预制形态。本课题组结合文献和前期研究结果分析认为，软骨诱导因子上调平滑肌肌动蛋白-α（SMA-α）表达很可能是导致ADSC构建软骨收缩形变的主要原因。本项目拟通过以慢病毒为载体的过表达技术和RNA干扰技术特异性上调或阻断SMA-α的表达，阐明SMA-α上调与ADSC构建软骨收缩形变之间的因果关系，在此基础上，优选出既能够抑制SMA-α表达又能协同软骨诱导的抗收缩因子对抗ADSC体外构建软骨过程中的收缩形变，探讨应用ADSC复合预制形态的支架材料体外构建组织工程鼻软骨的可行性，以期为临床鼻缺损的修复和重建提供自体软骨移植物。

组织工程技术是鼻软骨再生的一种全新手段,然而种子细胞问题限制了该技术的临床应用。脂肪来源干细胞(ADSC)在整形外科手术中来源丰富,取材创伤小,并具有软骨分化潜能,很适合临床推广应用。但是,ADSC-支架材料复合物在体外软骨诱导过程中很容易发生收缩形变,无法维持支架材料的预制形态。本课题组结合文献和前期研究结果分析 认为,软骨诱导因子上调平滑肌肌动蛋白-α(SMA-α)表达很可能是导致 ADSC 构建软骨收缩形变的主要原因。本项目通过以慢病毒为载体的过表达技术和RNA干扰技术特异性上调或阻断 SMA-α的表达,阐明了 SMA-α 上调与 ADSC 构建软骨收缩形变之间的因果关系,在此基础上,优选出既能够抑制 SMA-α表达又能协同软骨诱导的抗收缩因子对抗 ADSC 体外构建软骨过程中的收缩形变,并应用 ADSC 复合预制形态的支架材料体外构建组织工程鼻软骨,为临床鼻缺损的修复和重建提供自体软骨移植物。