一种新型3D预淋巴管化材料的制备及其治疗淋巴水肿效果的研究

Breast cancer related lymphedema (BCRL) is one of the common complications in the post-surgery patient and one of the most cause of secondary lymphedema. It may cause serious infection and even the amputation. Our project is supposed to develop a specific, quick and effective method to promote lymphatic system regeneration. In previous study, we produce lymphatic vessel-like structure with the use of BM-MSCs induced in hypoxia. Compared to BM-MSCs, adipose-derived stem cells (ADSCs) is easier to obtain and extract, more productive and has no significant correlation between cell differentiation ability, cell gain rate and age, which makes it as an ideal seed-cell to regenerate the lymphatic circulation system. In this project, highly aligned decellularized ECM, hypoxia induced ADSCs and bioreactor will be applied in the project to produce a 3D lymphatic engineering tissue. Optimization will be performed between BM-MSCs and ADSCs to select as “seed stem cells” in lymphatic tissue construction and the animal experiment will be performed to examine the application prospect of the tissue in vivo as well as the differentiation and possible mechanism of “seed stem cells” in treatment of the lymphedema. We suppose to provide a theoretical foundation and a promising therapeutic method in the lymphedema treatment.

乳腺癌术后上肢淋巴水肿(BCRL)是乳腺癌病人手术后常见的并发症之一，也是继发性淋巴水肿重要病因之一，可继发感染甚至截肢，严重影响患者的生活质量。本课题拟探索特异性、快速而有效地促进淋巴系统再生的方法。预实验显示低氧预处理骨髓间充质干细胞（BM-MSCs）在体外可以促进淋巴管形成。相较于BM-MSCs，脂肪干细胞（ADSCs）来源更广、分化能力和获取量与年龄无明显相关，因而是构建淋巴系统再生的重要种子细胞。本课题拟用高趋向性细胞外基质（ECM）、低氧预处理干细胞方法和生物反应器培养技术构建新型3D预淋巴管化组织材料，比较BM-MSCs和ADSCs成管情况以优化选择“种子干细胞”，体内实验验证其可应用性并探索“种子干细胞”在治疗淋巴水肿过程中可能的机制及转归，为临床治疗以BCRL为代表的淋巴水肿奠定应用基础、提供新的治疗思路。

淋巴管是人体脉管结构的重要组成部分。 但淋巴管的完整性被破坏、渗透性增加，局部组织处于水肿状态； TNF-α增强 LECs 的运动性并刺激巨噬细胞与LEC 的粘附，从而导致持续的炎症反应，这种病理性改变，可能是导致皮肤损伤后创面难以愈合的重要因素之一。 乳腺癌术后上肢淋巴水肿(BCRL)是乳腺癌病人手术后常见的并发症之一，也是继发性淋巴水肿重要病因之一，可继发感染甚至截肢，严重影响患者的生活质量。 因此探索特异性、快速而有效地促进淋巴系统再生的方法，具有重要的临床意义和转化应用前景。 .课题组在项目经费的资助下进行了下列研究：1）通过脂肪干细胞与淋巴管内皮细胞共培养构建了预淋巴管化干细胞组织；2）通过ELISA法测定培养体系内淋巴管生长因子的表达，初步探讨了淋巴管形成的机制；3）在体验证了预淋巴管化材料可以缓解急性淋巴水肿。课题组的上述研究成果将为防治淋巴水肿提供新的治疗策略和方法，具有一定转化应用潜能。