Organ injury stimulates the formation of new capillaries to restore blood supply raising questions about the potential contribution of neoangiogenic vessel architecture to the healing process. Using single -cell mapping, we resolved the properties of endothelial cells that organize a polarized scaffold at the repair site of lesioned peripheral nerves. Transient reactivation of an embryonic guidance program is required to orient neovessels across the wound. Manipulation of this structured angiogenic response through genetic and pharmacological targeting of Plexin-D1/VEGF pathways within an early window of repair has long-term impact on configuration of the nerve stroma. Neovessels direct nerve -resident mesenchymal cells to mold a provisionary fibrotic scar by assembling an orderly system of stable barrier compartments that channel regenerating nerve fibers and shield them from the persistently leaky vasculature. Thus, guided and balanced repair angiogenesis enables the construction of a "bridge"microenvironment conducive for axon regrowth and homeostasis of the regenerated tissue.

Structured wound angiogenesis instructs mesenchymal barrier compartments in the regenerating nerve / Bhat, Ganesh Parameshwar; Maurizio, Aurora; Motta, Alessia; Podini, Paola; Diprima, Santo; Malpighi, Chiara; Brambilla, Ilaria; Martins, Luis; Badaloni, Aurora; Boselli, Daniela; Bianchi, Francesca; Pellegatta, Marta; Genua, Marco; Ostuni, Renato; Del Carro, Ubaldo; Taveggia, Carla; de Pretis, Stefano; Quattrini, Angelo; Bonanomi, Dario. - In: NEURON. - ISSN 1097-4199. - 112:2(2024). [10.1016/j.neuron.2023.10.025]

Structured wound angiogenesis instructs mesenchymal barrier compartments in the regenerating nerve

Motta, Alessia;Brambilla, Ilaria;Ostuni, Renato;
2024-01-01

Abstract

Organ injury stimulates the formation of new capillaries to restore blood supply raising questions about the potential contribution of neoangiogenic vessel architecture to the healing process. Using single -cell mapping, we resolved the properties of endothelial cells that organize a polarized scaffold at the repair site of lesioned peripheral nerves. Transient reactivation of an embryonic guidance program is required to orient neovessels across the wound. Manipulation of this structured angiogenic response through genetic and pharmacological targeting of Plexin-D1/VEGF pathways within an early window of repair has long-term impact on configuration of the nerve stroma. Neovessels direct nerve -resident mesenchymal cells to mold a provisionary fibrotic scar by assembling an orderly system of stable barrier compartments that channel regenerating nerve fibers and shield them from the persistently leaky vasculature. Thus, guided and balanced repair angiogenesis enables the construction of a "bridge"microenvironment conducive for axon regrowth and homeostasis of the regenerated tissue.
2024
Semaphorin/Plexin
angiogenesis
blood-tissue barrier
cell guidance
mesenchymal cells
perineurium
regeneration
scarring
single-cell transcriptomics
would healing
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/158577
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