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Issue 20, 2016
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Impact of TNF and IL-1β on capillary networks within engineered human adipose tissues

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Abstract

Inflammation is a normal phase of the wound healing process, which likely occurs following tissue transplantation. For reconstructive surgery purposes, engineered adipose tissues represent promising alternatives to autologous fat grafts. It is therefore important to study the impact of an inflammatory microenvironment on the cellular functions of the different cell types comprised within matrix-rich reconstructed tissues. In this study, human reconstructed adipose tissues (hrATs) featuring a preformed capillary network formed by microvascular endothelial cells (hMVECs) were produced from adipose-derived stem/stromal cells (ASCs) by the self-assembly approach of tissue engineering. We hypothesized that a prolonged inflammatory context, mediated by tumor necrosis factor (TNF) and interleukin-1β (IL-1β), would impact hrATs' secretory profile and mediate detrimental effects on the microvascular network in vitro. Analysis of conditioned media established tissue responsiveness through the increased secretion of monocyte chemoattractant protein-1 (up to 23 fold), interleukin-6 (up to 69 fold) and angiopoietin-1 (up to 2.7 fold) after 3 and 6 days of cytokine exposure, along with a significant reduction in adiponectin secretion. Imaging of the preformed capillary network within the hrATs revealed increased disorganization in the presence of TNF/IL-1β, featuring a less extended and less ramified network with apoptotic hMVECs in the remaining capillary structures. These results indicate that a prolonged inflammatory context can be deleterious to the capillary network featured by in vitro engineered tissues. Strategies aiming at preserving the integrity of the vascular network will help develop substitutes that are better suited to face inflammatory conditions upon grafting.

Graphical abstract: Impact of TNF and IL-1β on capillary networks within engineered human adipose tissues

  • This article is part of the themed collection: Stem Cells
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Publication details

The article was received on 30 Jan 2016, accepted on 26 Apr 2016 and first published on 27 Apr 2016


Article type: Paper
DOI: 10.1039/C6TB00265J
Citation: J. Mater. Chem. B, 2016,4, 3608-3619
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    Impact of TNF and IL-1β on capillary networks within engineered human adipose tissues

    M. Proulx, M. Safoine, D. Mayrand, K. Aubin, A. Maux and J. Fradette, J. Mater. Chem. B, 2016, 4, 3608
    DOI: 10.1039/C6TB00265J

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