Cellular trans-differentiation and morphogenesis towards the lymphatic lineage in regenerative medicine

Lymphoedema is a medically irresolvable condition. The lack of therapies addressing lymphatic vessel dysfunction suggests that improved understanding of lymphatic cell differentiation and vessel maturation processes is key to the development of novel, regenerative medicine and tissue engineering approaches. In this review we provide an overview of lymphatic characterisation markers and morphology in development. Furthermore, we describe multiple differentiation processes of the lymphatic system during embryonic, post-natal and pathogenic development. Using the example of pathogenic Kaposi Sarcoma-associated Herpes infection we illustrate the involvement of the Notch and PI3K pathways for lymphatic trans-differentiation. We also discuss the plasticity of certain cell types and bio-factors which enable trans-differentiation towards the lymphatic lineage. Here we argue the importance of pathway-associated induction factors for lymphatic trans-differentiation including growth factors such as VEGF-C and interleukins, and the involvement of extracellular matrix characteristics and dynamics for morphological functionality.