A novel breast-cancer model of early stage invasion

The majority of breast cancer deaths are not caused by the primary tumor, but by metastasis to other organs. However, the mechanisms that underlie the first stage of metastasis, the invasion of cancer cells into surrounding tissue remain elusive, due to the complexity of the cellular, biochemical, and biophysical interactions in cancer tissue. \u3cbr/\u3e\u3cbr/\u3eIn this work, we propose a novel in vitro breast cancer model that focuses on dissecting the influence of the biophysical properties of the extracellular matrix (ECM) on the onset of cancer invasion. Based on microfluidic technology, it will provide us with the necessary tools to independently vary different material and cell properties, while it provides the cells with a physiologically relevant environment.\u3cbr/\u3

MDA-MB-231 breast cancer cells and their CSC population migrate towards low oxygen in a microfluidic gradient device

\u3cp\u3eMost cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.\u3c/p\u3

A novel breast cancer model of early stage invasion:using microfluidic methods to mimic a heterogeneous physical tumor microenvironment

The majority of breast cancer deaths are not caused by the primary tumor, but by metastasis to other organs. In this work, we propose a novel in vitro breast cancer model that focuses on dissecting the influence of the biophysical properties of the extracellular matrix (ECM) on the onset of cancer invasion. Based on microfluidic technology, it will provide us with the necessary tools to independently vary different material and cell properties, while it provides the cells with a physiologically relevant environment.\u3cbr/\u3

Metastasis in context:modeling the tumor microenvironment with cancer-on-a-chip approaches

\u3cp\u3eMost cancer deaths are not caused by the primary tumor, but by secondary tumors formed through metastasis, a complex and poorly understood process. Cues from the tumor microenvironment, such as the biochemical composition, cellular population, extracellular matrix, and tissue (fluid) mechanics, have been indicated to play a pivotal role in the onset of metastasis. Dissecting the role of these cues from the tumor microenvironment in a controlled manner is challenging, but essential to understanding metastasis. Recently, cancer-on-a-chip models have emerged as a tool to study the tumor microenvironment and its role in metastasis. These models are based on microfluidic chips and contain small chambers for cell culture, enabling control over local gradients, fluid flow, tissue mechanics, and composition of the local environment. Here, we review the recent contributions of cancer-on-a-chip models to our understanding of the role of the tumor microenvironment in the onset of metastasis, and provide an outlook for future applications of this emerging technology.\u3c/p\u3

Distinct contributions of astrocytes and pericytes to neuroinflammation identified in a 3D human blood-brain barrier on a chip

\u3cp\u3eNeurovascular inflammation is a major contributor to many neurological disorders, but modeling these processes in vitro has proven to be difficult. Here, we microengineered a three-dimensional (3D) model of the human blood-brain barrier (BBB) within a microfluidic chip by creating a cylindrical collagen gel containing a central hollow lumen inside a microchannel, culturing primary human brain microvascular endothelial cells on the gel's inner surface, and flowing medium through the lumen. Studies were carried out with the engineered microvessel containing endothelium in the presence or absence of either primary human brain pericytes beneath the endothelium or primary human brain astrocytes within the surrounding collagen gel to explore the ability of this simplified model to identify distinct contributions of these supporting cells to the neuroinflammatory response. This human 3D BBB-on-a-chip exhibited barrier permeability similar to that observed in other in vitro BBB models created with non-human cells, and when stimulated with the inflammatory trigger, tumor necrosis factor-alpha (TNF-α), different secretion profiles for granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were observed depending on the presence of astrocytes or pericytes. Importantly, the levels of these responses detected in the 3D BBB chip were significantly greater than when the same cells were co-cultured in static Transwell plates. Thus, as G-CSF and IL-6 have been reported to play important roles in neuroprotection and neuroactivation in vivo, this 3D BBB chip potentially offers a new method to study human neurovascular function and inflammation in vitro, and to identify physiological contributions of individual cell types.\u3c/p\u3

Compression and reswelling of microgel particles after an osmotic shock

We use dedicated microfluidic devices to expose soft hydrogel particles to a rapid change in the externally applied osmotic pressure and observe a surprising, non-monotonic response: After an initial rapid compression, the particle slowly reswells to approximately its original size. We theoretically account for this behavior, enabling us to extract important material properties from a single microfluidic experiment, including the compressive modulus, the gel permeability, and the diffusivity of the osmolyte inside the gel. We expect our approach to be relevant to applications such as controlled release, chromatography, and responsive materials