Lymph Node Subcapsular Sinus Microenvironment-On-A-Chip Modeling Shear Flow Relevant to Lymphatic Metastasis and Immune Cell Homing

Abstract

Summary A lymph node sinus-on-a-chip adhesion microfluidic platform that recapitulates the hydrodynamic microenvironment of the lymph node subcapsular sinus was engineered. This device was used to interrogate the effects of lymph node remodeling on cellular adhesion in fluid flow relevant to lymphatic metastasis. Wall shear stress levels analytically estimated and modeled after quiescent and diseased/inflamed lymph nodes were experimentally recapitulated using a flow-based microfluidic perfusion system to assess the effects of physiological flow fields on human metastatic cancer cell adhesion. Results suggest that both altered fluid flow profiles and presentation of adhesive ligands, which are predicted to manifest within the lymph node subcapsular sinus as a result of inflammation-induced remodeling, and the presence of lymph-borne monocytic cells may synergistically contribute to the dynamic extent of cell adhesion in flow relevant to lymph node invasion by cancer and monocytic immune cells during lymphatic metastasis.

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

“…developed a LN subcapsular sinus-on-a-chip that recreated the LN hydrodynamic microenvironment and the effect of wall shear stress ( Fig. 4 A) [ 206 ]. They found that cell motility and adhesion are critical to immune cell recruitment and cancerous metastasis in the LN.…”

“…A) Schematic illustration of a subcapsular sinus microenvironment-mimicking, divergent parallel-plate microfluidic perfusion with an adhesion-molecule-functionalized, divergent portion. Reproduced with permission [ 206 ]. Copyright 2020, Elsevier.…”

Lymph Nodes-On-Chip: Promising Immune Platforms for Pharmacological and Toxicological Applications

“…The source of the cellular components is also an important point to consider. Some devices are validated using immortalized human cell lines as they are easy to obtain, manipulate and expand, are cost effective and allow experimental reproducibility (Moura Rosa et al, 2016;Birmingham et al, 2020;Shanti et al, 2020;Hallfors et al, 2021). Cell lines are well established models that can be easily modified to target and study molecules of interest.…”

“…In a different attempt, Birmingham et al developed a novel microfluidic device to investigate the effect of subcapsular sinus remodeling (seen in inflammation) both biophysically (flow and structure) and biochemically (adhesion molecule expression) on human monocytic and metastatic cellular adhesion (Birmingham et al, 2020). The microfluidic device consists of a divergent adhesive microchannel cut from a 125 mm thick double sided adhesive tape and affixed to a PDMS block previously cured in a polystyrene tissue culture plate.…”

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

“…Conversely, other studies have revealed a pro-tumoral effect of these cells, mainly linked with their capacity to trigger and maintain the inflammatory response both in peripheral and lymphoid tissues 9,30,31 .…”