TY - JOUR A1 - Trisko, Johanna A1 - Fleck, Johanna A1 - Kau, Silvio A1 - Oesterreicher, Johannes A1 - Holnthoner, Wolfgang T1 - Lymphatic and Blood Endothelial Extracellular Vesicles: A Story Yet to Be Written JF - Life N2 - Extracellular vesicles (EVs), such as exosomes, microvesicles, and apoptotic bodies, are cell-derived, lipid bilayer-enclosed particles mediating intercellular communication and are therefore vital for transmitting a plethora of biological signals. The vascular endothelium substantially contributes to the circulating particulate secretome, targeting important signaling pathways that affect blood cells and regulate adaptation and plasticity of endothelial cells in a paracrine manner. Different molecular signatures and functional properties of endothelial cells reflect their heterogeneity among different vascular beds and drive current research to understand varying physiological and pathological effects of blood and lymphatic endothelial EVs. Endothelial EVs have been linked to the development and progression of various vascular diseases, thus having the potential to serve as biomarkers and clinical treatment targets. This review aims to provide a brief overview of the human vasculature, the biology of extracellular vesicles, and the current knowledge of endothelium-derived EVs, including their potential role as biomarkers in disease development. KW - Tissue Engineering KW - Endothelial Cells KW - vascularization KW - extracellular vesicles KW - lymphatic endothelial cells Y1 - VL - 2022 IS - 12(5) SP - 654 ER - TY - JOUR A1 - Hromada, Carina A1 - Hartmann, Jaana A1 - Oesterreicher, Johannes A1 - Stoiber, Anton A1 - Daerr, Anna A1 - Schädl, Barbara A1 - Priglinger, Eleni A1 - Teuschl-Woller, Andreas H. A1 - Holnthoner, Wolfgang A1 - Heinzel, Johannes Christoph A1 - Hercher, David T1 - Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-Induced Apoptosis of Lymphatic Endothelial Cells In Vitro JF - Biomolecules N2 - Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types' migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC-LEC interaction. KW - Tissue Engineering KW - peripheral nerve regeneration KW - lymphangiogenesis KW - Schwann cells KW - lymphatic endothelial cells Y1 - VL - 2022 IS - 12, 6 SP - 820 ER -