脂肪干细胞通过外泌体miRNA对瘢痕疙瘩成纤维细胞的调控作用研究

Keloid is one of the common diseases of plastic and reconstructive surgery, until now, there is still not an ideal treatment for keloid that is safe and has long-lasting outcome. Recently, people found the inhibition ability of adipose-derived stem cells(ASCs) on scar tissue, but the mechanism of which is unclear. We speculate that exosomes secreted by the ASCs may play an important part in the regulation of keloid fibroblasts. In our previous experiment we have proved that ASCs secreted exosomes, which could directly inhibit the keloid fibroblasts collagen synthesis. Meanwhile studies have demonstrated important regulatory roles of miRNAs in the development of fibrosis and keloids. Therefore, our hypothesis is that the ASCs may secret exosomes carrying miRNAs that regulate the proliferation and function of keloid, which may be a possible cell-therapy on keloid. To further prove our hypothesis, we focus on the ASCs exosomes, analyze and screen out the possible miRNAs that take part in the regulation of keloid fibroblasts proliferation, migration, fibrosis and collagen synthesis, thus we can provide theoretical and experimental basis for the cell therapy of keloids.

瘢痕疙瘩是整形外科的常见疾病，目前仍缺乏一种效果可靠、副作用小的治疗方法。近年来研究发现脂肪干细胞具有抑制瘢痕增生的作用，但作用机制尚不明确。我们推测外泌体的分泌及其对成纤维细胞的调控可能是脂肪干细胞治疗瘢痕的作用机制之一。在前期实验中我们证实了脂肪干细胞外泌体的存在，并能对瘢痕疙瘩成纤维细胞的胶原分泌功能产生抑制作用。结合多项关于miRNA在组织纤维化和病理性瘢痕中起重要作用的报道，我们提出假说，脂肪干细胞可以通过外泌体中运载的miRNA对瘢痕疙瘩成纤维细胞的活性和功能进行调控，具有干细胞治疗瘢痕疙瘩的应用前景。为了验证这一假说，本课题拟通过对脂肪干细胞分泌的外泌体进行研究，特别是外泌体中miRNA对瘢痕疙瘩成纤维细胞增殖、迁徙、纤维化和胶原合成等相关基因表达的影响进行分析，明确脂肪干细胞外泌体中调控瘢痕疙瘩成纤维细胞的关键miRNA，为应用干细胞治疗瘢痕疙瘩提供理论依据和实验基础。

在此项目的研究中，本人负责的课题组紧紧围绕人脂肪组织来源干细胞外泌体miRNA对于瘢痕疙瘩成纤维细胞的调控作用这条主线，对人脂肪干细胞外泌体并进行了鉴定和分析；研究了外泌体作用后瘢痕疙瘩成纤维细胞中与细胞增殖、迁徙、纤维化和胶原合成等相关基因表达的变化；筛选出了在脂肪干细胞外泌体中存在的能够调控成纤维细胞活性和功能的miRNA；并利用基因调控后脂肪干细胞外泌体miRNA实现了对瘢痕疙瘩成纤维细胞的调控作用。目前该课题的研究成果已经作为干细胞瘢痕治疗的理论基础之一，已经有十余位瘢痕疙瘩患者得到了新技术的帮助。