Fibroblasts mediate endothelium response to angiogenic cues in a newly developed 3D stroma engineered model.

Autor: Dellaquila A; Université Paris Cité, Université Sorbonne Paris Nord, Laboratory for Vascular Translational Science, INSERM U1148, X. Bichat Hospital, Paris 75018, France. Electronic address: alessandra.dellaquila@inserm.fr., Dujardin C; Université Paris Cité, Université Sorbonne Paris Nord, Laboratory for Vascular Translational Science, INSERM U1148, X. Bichat Hospital, Paris 75018, France., Le Bao C; Université Paris Cité, Université Sorbonne Paris Nord, Laboratory for Vascular Translational Science, INSERM U1148, X. Bichat Hospital, Paris 75018, France., Chaumeton C; Sorbonne Université, Institute of Biology Paris-Seine, Paris 75005, France., Carré A; Université Paris Cité, Université Sorbonne Paris Nord, Laboratory for Vascular Translational Science, INSERM U1148, X. Bichat Hospital, Paris 75018, France., Le Guilcher C; Université Paris Cité, Université Sorbonne Paris Nord, Laboratory for Vascular Translational Science, INSERM U1148, X. Bichat Hospital, Paris 75018, France., Lam F; Sorbonne Université, Institute of Biology Paris-Seine, Paris 75005, France., Simon-Yarza T; Université Paris Cité, Université Sorbonne Paris Nord, Laboratory for Vascular Translational Science, INSERM U1148, X. Bichat Hospital, Paris 75018, France. Electronic address: teresa.simon-yarza@inserm.fr.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2023 Nov; Vol. 154, pp. 213636. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1016/j.bioadv.2023.213636
Abstrakt: Three-dimensional stroma engineered models would enable fundamental and applicative studies of human tissues interaction and remodeling in both physiological and pathological conditions. In this work, we propose a 3D vascularized stroma model to be used as in vitro platform for drug testing. A pullulan/dextran-based porous scaffold containing pre-patterned microchannels of 100 μm diameter is used for co-culturing of fibroblasts within the matrix pores and endothelial cells to form the lumen. Optical clearing of the constructs by hyperhydration allows for in-depth imaging of the model up to 1 mm by lightsheet and confocal microscopy. Our 3D vascularized stroma model allows for higher viability, metabolism and cytokines expression compared to a monocultured vascular model. Stroma-endothelium cross-talk is then investigated by exposing the system to pro and anti-angiogenic molecules. The results highlight the protective role played by fibroblasts on the vasculature, as demonstrated by decreased cytotoxicity, restoration of nitric oxide levels upon challenge, and sustained expression of endothelial markers CD31, vWF and VEGF. Our tissue model provides a 3D engineered platform for in vitro studies of stroma remodeling in angiogenesis-driven events, known to be a leading mechanism in diseased conditions, such as metastatic cancers, retinopathies and ischemia, and to investigate related potential therapies.
Competing Interests: Declaration of competing interest The authors declare no competing financial interests nor personal relationships that could have influenced the work reported here.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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