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Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-induced Apoptosis of Lymphatic Endothelial Cells in vitro

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Submitted:

20 May 2022

Posted:

23 May 2022

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Abstract
Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in case of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly underinvestigated. 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 do 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 to elucidate the molecular mechanisms of SC-LEC interaction.
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Subject: Medicine and Pharmacology  -   Neuroscience and Neurology
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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