In vitro microfluidic model for the study of vaso-occlusive processes

Dominical, Venina Marcela; Vital, Daiana Morelli; O'Dowd, Frank; Saad, Sara T. Olalla; Costa, Fernando Ferreira; Conran, Nicola

doi:10.1016/j.exphem.2014.10.015

Cited by 20 publications

(25 citation statements)

References 27 publications

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“…When culturing cells in vitro we should update the culture conditions to closely match those of a specific tissue environment. This can be something simple, such as including retinoic acid for pResMϕ culture or transforming growth factor β 1 for microglial culture, using physiologically relevant oxygen levels, or providing microfluidic flow to retain phenotype ex vivo . However, this is destined to become more advanced with increased understanding of tissue environments.…”

Section: Development Of a New Paradigmmentioning

confidence: 99%

Tissue‐resident macrophages: then and now

2015

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Macrophages have been at the heart of immune research for over a century and are an integral component of innate immunity. Macrophages are often viewed as terminally differentiated monocytic phagocytes. They infiltrate tissues during inflammation, and form polarized populations that perform pro-inflammatory or anti-inflammatory functions. Tissue-resident macrophages were regarded as differentiated monocytes, which seed the tissues to perform immune sentinel and homeostatic functions. However, tissue-resident macrophages are not a homogeneous population, but are in fact a grouping of cells with similar functions and phenotypes. In the last decade, it has been revealed that many of these cells are not terminally differentiated and, in most cases, are not derived from haematopoiesis in the adult. Recent research has highlighted that tissue-resident macrophages cannot be grouped into simple polarized categories, especially in vivo, when they are exposed to complex signalling events. It has now been demonstrated that the tissue environment itself is a major controller of macrophage phenotype, and can influence the expression of many genes regardless of origin. This is consistent with the concept that cells within different tissues have diverse responses in inflammation. There is still a mountain to climb in the field, as it evolves to encompass not only tissue-resident macrophage diversity, but also categorization of specific tissue environments and the plasticity of macrophages themselves. This knowledge provides a new perspective on therapeutic strategies, as macrophage subsets can potentially be manipulated to control the inflammatory environment in a tissue-specific manner.

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Section: Development Of a New Paradigmmentioning

confidence: 99%

Tissue‐resident macrophages: then and now

2015

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“…9 Several studies have used polydimethylsiloxane (PDMS; Silicone) based microfluidic assays to extract invaluable insight into the mechanism of vaso-occlusion. However, these approaches were limited by the use of isolated SS-RBCs 10 or the inability to visualize cellular interactions at single cell resolution 11 and distinguish different cell types that constitute the vaso-occlusive plug. 8 We introduce qMFM (Figure 1), which enables visualization of molecular interactions between neutrophils and platelets at single cell resolution in SS blood.…”

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confidence: 99%

Quantitative microfluidic fluorescence microscopy to study vaso-occlusion in sickle cell disease

et al. 2015

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“…Simplified microfluidic models use isolated integrin antibodies or ECM proteins to determine their influence on cellular interactions and blood flow . The SCD biochip consists of laminin or E‐selectin‐coated channels with diameters comparable to microvasculature diameters, 10‐40 μm . Neutrophils derived from SCD patients adhered to channels at a greater rate than neutrophils from healthy individuals.…”

Section: Microfluidics: Biomarkers Mechanisms and Therapeuticsmentioning

confidence: 99%

“…Interestingly, SCD RBCs alone did not significantly adhere to or occlude the microchannels within the biochip. However, mixing SCD neutrophils and RBCs led to occlusions in the laminin‐coated channels suggesting that leukocytes mediate vaso‐occlusion processes . Microfluidic devices have the sensitivity to detect the differences between healthy and diseased blood samples based on cellular mechanical properties and behavior.…”

Section: Microfluidics: Biomarkers Mechanisms and Therapeuticsmentioning

confidence: 99%

Microfluidics for investigating vaso‐occlusions in sickle cell disease

Horton

2017

Microcirculation

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SCD stems from amutation in the beta globin gene. Upon deoxygenation, hemoglobin polymerizes and triggers RBC remodeling. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications; unfortunately, the complex mechanisms that contribute to vaso-occlusions are not well understood. Vaso-occlusions can occur in post-capillary venules; hence, the microvasculature is a prime target for SCD therapies. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivo systems. However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and ECM presentation. This review, although not comprehensive, highlights microfluidic approaches that aim to improve our current understanding of the pathophysiological mechanisms surrounding SCD. Microfluidic platforms can aid in identifying factors that may contribute to disease severity and can serve as suitable test beds for novel treatment strategies which may improve patient outcomes.

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In vitro microfluidic model for the study of vaso-occlusive processes

Cited by 20 publications

References 27 publications

Tissue‐resident macrophages: then and now

Tissue‐resident macrophages: then and now

Quantitative microfluidic fluorescence microscopy to study vaso-occlusion in sickle cell disease

Microfluidics for investigating vaso‐occlusions in sickle cell disease

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