| Autor: |
Serena Zacchigna, Roman Vuerich, Elena Groppa, Simone Vodret, Nadja Ring, Matteo Cauteruccio, Andrea Colliva, Francesca Simoncello, Federica Benvenuti, Chiara Stocco, Fleur Bossi, Chiara Agostinis, Anna Agnelli, Franca Dore, Silvia Palmisano, Nicolo' De Manzini, Roberta Bulla, Giovanni Papa, Flavia Mazzarol, Massimo Moretti, Alice Paulitti, Mattia Chiesa, Giulio Pompilio |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1857786/v1 |
| Popis: |
With the increased prevalence of chronic diseases, non-healing wounds place a significant burden on both the quality of life of affected patients and health systems. Skin substitutes are applied to promote the closure of non-healing wounds, although their efficacy is limited by inadequate vascularization. The stromal vascular fraction (SVF) from the adipose tissue has emerged as 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 new model of non-healing wound, in which we applied the SVF in combination with a clinical grade skin substitute. First, 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 of both species. Also in this case, these vessels were connected with the host circulatory system and determined a 2-fold increase in tissue perfusion. 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 non-healing wounds. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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