Real-time observation of leukocyte–endothelium interactions in tissue-engineered blood vessel

Abstract

Human cell-based 3D tissue constructs play an increasing role in disease modeling and drug screening. Inflammation, atherosclerosis, and many autoimmune disorders involve the interactions between immune cells and blood vessels. However, it has been difficult to image and model these interactions under realistic conditions. In this study, we fabricated a perfusion and imaging chamber to allow the real-time visualization of leukocyte perfusion, adhesion, and migration inside a tissue-engineered blood vessel (TEBV). We monitored the elevated monocyte adhesion to the TEBV wall and transendothelial migration (TEM) as the TEBV endothelium was activated by the inflammatory cytokine TNF-α. We demonstrated that treatment with anti-TNF-α or an NF-kB signaling pathway inhibitor would attenuate the endothelium activation and reduce the number of leukocyte adhesion (>74%) and TEM events (>87%) close to the control. As the first demonstration of real-time imaging of dynamic cellular events within a TEBV, this work paves the way for drug screening and disease modeling in TEBV-associated microphysiological systems.

Emulating Early Atherosclerosis in a Vascular Microphysiological System Using Branched Tissue‐Engineered Blood Vessels

“…The MCs not only adhered but also changed morphology (yellow arrows in Figure 2c), implicating potential transvasation into the vessel wall to form foam cells in vivo. [33] Foam cell formation following MC adhesion was also investigated. The brTEBVs were perfused for at least 7 days for maturation before treatment with eLDL for 3 days and with TNF-α for 12 h, followed by perfusion with THP-1 MCs for 3 days.…”

Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature

“…Indeed, inflamed neutrophils injected in a microvascular network model aggregated with circulating melanoma cells, facilitating the adhesion of cancer cells to endothelial cells. The confinement of these aggregates to the endothelium was favored by the secretion of IL8 from neutrophils and correlated with a higher extravasation of cancer cells (Chen et al, 2018 ).…”

Biocasting of an elastin-like recombinamer and collagen bi-layered model of the tunica adventitia and external elastic lamina of the vascular wall

“…The presence of microfibrils intertwined with the elastin 84 , along with the accompanying cells, collagen and the thin conformation found for the internal and external elastic laminae 6 , seems to compromise the extensibility of the native tissue, thus resulting in the large difference found with the bi-layered models manufactured herein. The ELR layer not only serves for reproducing the commonly overlooked ELL [85][86][87] but also offers a tailorable scaffold for including bioactive domains able to modulate the cell behavior towards a physiological-like vascular wall model. Here, embedded HDF appear to respond to the cell-adhesive and proteolytic sites encoded in the ELR matrix.…”