Ischemic wound revascularization by the stromal vascular fraction relies on host-donor hybrid vessels
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Published:2023-02-11
Issue:1
Volume:8
Page:
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ISSN:2057-3995
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Container-title:npj Regenerative Medicine
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language:en
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Short-container-title:npj Regen Med
Author:
Vuerich RomanORCID, Groppa Elena, Vodret Simone, Ring Nadja Annelies Ruth, Stocco Chiara, Bossi Fleur, Agostinis ChiaraORCID, Cauteruccio Matteo, Colliva Andrea, Ramadan MohammadORCID, Simoncello Francesca, Benvenuti Federica, Agnelli Anna, Dore Franca, Mazzarol Flavia, Moretti Massimo, Paulitti Alice, Palmisano SilviaORCID, De Manzini Nicolò, Chiesa MattiaORCID, Casaburo Manuel, Raucci Angela, Lorizio Daniela, Pompilio Giulio, Bulla Roberta, Papa Giovanni, Zacchigna SerenaORCID
Abstract
AbstractNonhealing wounds place a significant burden on both quality of life of affected patients and health systems. Skin substitutes are applied to promote the closure of nonhealing wounds, although their efficacy is limited by inadequate vascularization. The stromal vascular fraction (SVF) from the adipose tissue is a promising therapy to overcome this limitation. Despite a few successful clinical trials, its incorporation in the clinical routine has been hampered by their inconsistent results. All these studies concluded by warranting pre-clinical work aimed at both characterizing the cell types composing the SVF and shedding light on their mechanism of action. Here, we established a model of nonhealing wound, in which we applied the SVF in combination with a clinical-grade skin substitute. We purified the SVF cells from transgenic animals to trace their fate after transplantation and observed that it gave rise to a mature vascular network composed of arteries, capillaries, veins, as well as lymphatics, structurally and functionally connected with the host circulation. Then we moved to a human-in-mouse model and confirmed that SVF-derived endothelial cells formed hybrid human-mouse vessels, that were stabilized by perivascular cells. Mechanistically, SVF-derived endothelial cells engrafted and expanded, directly contributing to the formation of new vessels, while a population of fibro-adipogenic progenitors stimulated the expansion of the host vasculature in a paracrine manner. These data have important clinical implications, as they provide a steppingstone toward the reproducible and effective adoption of the SVF as a standard care for nonhealing wounds.
Funder
ERDF POR FESR FVG Region
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Developmental Biology,Biomedical Engineering,Medicine (miscellaneous)
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