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Regeneration of the wound healing sites basing on the molecular analysis and the tissue-engineered

基于分子分析和组织工程的伤口愈合部位再生

基本信息

批准号：
13307051
负责人：
FUJII Tohru
金额：
$ 8.4万
依托单位：
NAGASAKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

For the successful regeneration of the wound healing sites, the molecular analysis and tissue-engineering methods are applied. Firat, the excessive wound healing such as keloids was analyzed with the signal transduction of the production of the extracelluar matrices. The TGF-./p38/ATF-2 signaling was most likely involved in the pathogenesis of the keloids. Then, the axial flap model was used for the possible cytokine and its receptor regulation on flap survival. The flap survival was significantly improved by cytokine-receptor modulation via flap axial vessels. The somatic stem cell in vitro investigation was focused on the early phase proliferation and differentiation. The cell proliferation, cell cycle regulation, histological findings and the ultrastructure of the bone marrow-derived human stem cells treated by basic fibroblast growth factor and bone morphogenetic protein-2 demonstrated the early phase growth of the human stemcells. Finally the in vivo use of the stem cell-mediated wound coverage was examined with an artificial skin substitute as a template. The stem cells treated with basic fibroblast growth factor were significantly healed in the nude rat skin defect model and the epithelization was suggested the stem cell-mediated mesenchymal to epithelial cell differentiation. The stem cells are beneficial for the cutaneous wound healing and possible clinical application for the difficult wound environment.

为了使创面愈合部位成功再生，应用了分子分析和组织工程方法。首先，用细胞外基质产生的信号转导来分析瘢痕疙瘩等过度创伤愈合。TGF-./ p38/ATF-2信号通路可能参与瘢痕疙瘩的发病机制。然后，利用轴型皮瓣模型研究细胞因子及其受体对皮瓣成活的可能调控作用。通过皮瓣轴向血管调节肾上腺素受体可显著提高皮瓣成活率。体干细胞的体外研究主要集中在早期增殖和分化方面。经碱性成纤维细胞生长因子和骨形态发生蛋白-2处理的人骨髓源性干细胞的细胞增殖、细胞周期调控、组织学观察和超微结构观察表明，人骨髓源性干细胞处于早期生长阶段。最后，以人工皮肤替代物为模板，研究了干细胞介导的伤口覆盖的体内使用。用碱性成纤维细胞生长因子处理的干细胞在裸鼠皮肤缺损模型中显著愈合，并且上皮化表明干细胞介导的间充质细胞向上皮细胞分化。干细胞对皮肤创伤的愈合有一定的促进作用，有望在复杂的创伤环境中应用于临床。