Kilarski Witold W
Institute for Molecular Engineering, The University of Chicago, Chicago, Illinois.
Adv Wound Care (New Rochelle). 2018 Jul 1;7(7):189-208. doi: 10.1089/wound.2017.0768.
Growth of distinctive blood vessels of granulation tissue is a central step in the post-developmental tissue remodeling. Even though lymphangiogenesis is a part of the regeneration process, the significance of the controlled restoration of lymphatic vessels has only recently been recognized. Identification of lymphatic markers and growth factors paved the way for the exploration of the roles of lymphatic vessels in health and disease. Emerging pro-lymphangiogenic therapies use vascular endothelial growth factor (VEGF)-C to combat fluid retention disorders such as lymphedema and to enhance the local healing process. The relevance of recently identified lymphatic functions awaits verification by their association with pathologic conditions. Further, despite a century of research, the complete etiology of secondary lymphedema, a fluid retention disorder directly linked to the lymphatic function, is not understood. Finally, the specificity of pro-lymphangiogenic therapy depends on VEGF-C transfection efficiency, dose exposure, and the age of the subject, factors that are difficult to standardize in a heterogeneous human population. Further research should reveal the role of lymphatic circulation in internal organs and connect its impairment with human diseases. Pro-lymphangiogenic therapies that aim at the acceleration of tissue healing should focus on the controlled administration of VEGF-C to increase their capillary specificity, whereas regeneration of collecting vessels might benefit from balanced maturation and differentiation of pre-existing lymphatics. Unique features of pre-nodal lymphatics, fault tolerance and functional hyperplasia of capillaries, may find applications outreaching traditional pro-lymphangiogenic therapies, such as immunomodulation or enhancement of subcutaneous grafting.
肉芽组织中独特血管的生长是发育后组织重塑的核心步骤。尽管淋巴管生成是再生过程的一部分，但淋巴管受控修复的重要性直到最近才被认识到。淋巴管标志物和生长因子的鉴定为探索淋巴管在健康和疾病中的作用铺平了道路。新兴的促淋巴管生成疗法使用血管内皮生长因子（VEGF）-C来对抗诸如淋巴水肿等液体潴留障碍，并促进局部愈合过程。最近发现的淋巴管功能的相关性有待通过它们与病理状况的关联来验证。此外，尽管经过了一个世纪的研究，但与淋巴管功能直接相关的液体潴留障碍——继发性淋巴水肿的完整病因仍不清楚。最后，促淋巴管生成疗法的特异性取决于VEGF-C的转染效率、剂量暴露和受试者的年龄，这些因素在异质的人群中难以标准化。进一步的研究应揭示淋巴循环在内部器官中的作用，并将其损伤与人类疾病联系起来。旨在加速组织愈合的促淋巴管生成疗法应专注于VEGF-C的可控给药以提高其毛细血管特异性，而集合淋巴管的再生可能受益于现有淋巴管的平衡成熟和分化。结前淋巴管的独特特征、毛细血管的容错性和功能增生，可能会在超越传统促淋巴管生成疗法的领域得到应用，如免疫调节或增强皮下移植。
