Lymphatic/blood vessel plasticity: motivation for a future research area based on present and past observations

The lymphatic system plays a significant role in homeostasis and drainage of excess fluid back into venous circulation. Lymphatics are also associated with a number of diseases including lymphedema, tumor metastasis, and various lymphatic mal-formations. Emerging evidence suggests that lymphatics might have a bigger connection to the blood vascular system than orig-inally presumed. As these two systems are often studied in isolation, several knowledge gaps exist surrounding what constitutes lymphatic vascular plasticity, under what conditions it arises, and where structures characteristic of plasticity can form. The objec-tive of this review is to overview current structural, cell lineage-based, and cell identity-based evidence for lymphatic plasticity. These examples of plasticity will then be considered in the context of potential clinical and surgical implications of this evolving research area. This review details our current understanding of lymphatic plasticity, highlights key unanswered questions in the field, and motivates future research aimed at clarifying the role and therapeutic potential of lymphatic plasticity in disease.