骨髓间充质干细胞促进扩张皮肤新生的机制及基因干预研究

皮肤软组织扩张术是整形外科最常用修复方法之一，但目前仍存在扩张时间较长的突出缺点，主要由于真皮成纤维细胞增殖较慢，细胞外基质合成速度慢，生物性生长产生新生皮肤速度较慢。本课题组前期在小额探索项目资助下，证实了扩张皮肤中约17%新生细胞来源于骨髓间充质干细胞（BM-MSCs），进一步筛查发现BM-MSCs可分泌大量色素上皮衍生因子（PEDF），PEDF可显著促进成纤维细胞增殖及移行，促伤口愈合，故我们推测：BM-MSCs在扩张皮肤局部通过旁分泌PEDF，促进真皮成纤维增殖。本研究拟利用腺病毒过表达及siRNA阻断BM-MSCs中PEDF表达，利用体外真皮成纤维细胞与BM-MSCs共培养模型及小鼠背部皮肤扩张模型，探索PEDF在BM-MSCs促进真皮成纤维细胞增殖及皮肤扩张过程中是否发挥重要作用及相关机制，为采用基因干预手段提高皮肤软组织扩张干细胞治疗效果提供分子靶点和理论依据。

Skin and soft tissue expansion therapy is widely used in plastic surgery, with an obvioius shortcoming of long-time expansion, due to the relatively slow proliferation of dermal fibroblasts and insufficient collagen secretion. Surported by a previous Small Exploration Project, we discovered that 17 percents of the new cells in the expanded skin were bone marrow-derived mesenchymal stem cells (BM-MSCs). Moreover, BM-MSCs can secrete PEDF, which can enhance the proliferation and migration of fibroblasts and wound healing. Therefore, we assumed that in the expanded skin BM-MSCs paracrine PEDF, promoting dermal fibroblasts proliferation. Based on the in vitro cell co-culture model and in vivo skin expansion model, via overexpressing PEDF by adenovirus and blocking PEDF expression by siRNA, we will investigate whether PEDF has an important effect on the process of skin expansion promoted by BM-MSCs and the mechanisms involved, which will provide a critical molecular target and theoretical basis for stem cell therapy in skin and soft tissue expansion.