骨髓间充质干细胞调控M2型巨噬细胞极化促进扩张皮肤生物性增长的应用基础研究

Skin and soft tissue expansion therapy is widely applied for repair in plastic surgery. How to obtain new skin tissue in the short time to repair the defect is urgent to solve in the clinical application. Many reports and our previous studies have shown that exogenous of bone marrow mesenchymal stem cells (BMSCs) participated in the regeneration of expanded skin. But the participation and mechanism is still not clear. Recently, we found the types of macrophage in the expanded skin were significantly changed at different phases. These indicated that the process of skin expansion is an injury and repair repeated process. The mechanism of regeneration is mainly through promotion the proliferation of vascular endothelial cell, fibroblasts proliferation and collagen synthesis. Based on these results, we will investigate the role of BMSCs regulation macrophage polarization in the expanded and reveal the molecular mechanism of regenerated skin. Also, we will clarify the mechanism and function of macrophage polarization in proliferation of vascular endothelial cell and dermal fibroblasts. Furthermore, we will reveal the function of JAK/STAT signaling pathway with macrophage polarization. These studies expand the understanding of the regulation mechanism of macrophage polarization in the skin, and provide the theoretical basis for improvement the efficiency of expansion skin in the clinical treatment.

皮肤软组织扩张术是整形外科最常用的治疗手段之一，短时间内获得用于修复缺损部位的新生皮肤组织是临床应用亟待解决的问题。大量文献和我们前期的研究表明，外源输入的骨髓间充质干细胞（BMSCs）参与了扩张皮肤的新生过程，但其参与方式和机制仍不清楚。最近我们对扩张皮肤中的巨噬细胞类型进行了初步探索,发现在不同时相的小鼠扩张皮肤中巨噬细胞的类型发生明显变化，证明了皮肤扩张是一个反复损伤和修复重建的过程，它主要通过促进血管内皮细胞增殖，成纤维细胞增殖以及胶原蛋白合成达到皮肤新生的目的。本课题拟在此研究基础上，深入研究BMSCs在皮肤扩张中调控巨噬细胞极化及参与皮肤新生的分子机制；揭示巨噬细胞极化在血管内皮细胞和真皮成纤维细胞增殖中的作用和机制；阐明JAK/STAT信号通路在巨噬细胞极化过程中的功能和意义。这些研究拓展了对皮肤中巨噬细胞极化调控机制的认识，同时为临床上提高皮肤软组织扩张效率提供理论依据。

皮肤软组织扩张术是整形外科最常用的治疗手段之一，短时间内获得用于修复缺损部位的新生皮肤组织是临床应用亟待解决的问题。最近我们对扩张皮肤中的巨噬细胞类型进行了初步探索,发现在不同时相的小鼠扩张皮肤中巨噬细胞的类型发生明显变化，证明了皮肤扩张是一个反复损伤和修复重建的过程，它主要通过促进血管内皮细胞增殖，成纤维细胞增殖以及胶原蛋白合成达到皮肤新生的目的。本课题拟在此研究基础上，深入阐明巨噬细胞在扩张皮肤中的表达及其对扩张皮肤新生的影响，研究去分化脂肪干细胞（DFATs）在皮肤扩张中调控巨噬细胞极化及参与皮肤新生的分子机制；并研究了色素上皮衍生因子（PEDF）在皮肤扩张中通过调控巨噬细胞极化影响成纤维细胞胶原的合成。这些研究拓展了对皮肤中巨噬细胞极化调控机制的认识，同时为临床上提高皮肤软组织扩张效率的治疗靶点提供理论依据。