scholarly journals Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

2021 ◽  
Author(s):  
Barbara Bachmann ◽  
Sarah Spitz ◽  
Christian Jordan ◽  
Patrick Schuller ◽  
Heinz D Wanzenboeck ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Immune Cell ◽  
Scientific Progress ◽  
Morphological Characteristics ◽  
Interstitial Fluid Flow

After decades of simply being referred to as the body's sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for cancer, infections, and inflammatory diseases. However, the lack of cell-based assays capable of recapitulating the required biological complexity combined with unreliable in vivo animal models currently hamper scientific progress in lymph-targeted drug delivery. To gain more in-depth insight into the blood-lymph interface, we established an advanced chip-based microvascular model to study mechanical stimulation's importance on lymphatic sprout formation. Our microvascular model's key feature is the co-cultivation of spatially separated 3D blood and lymphatic vessels under controlled, unidirectional interstitial fluid flow while allowing signaling molecule exchange similar to the in vivo situation. We demonstrate that our microphysiological model recreates biomimetic interstitial fluid flow, mimicking the route of fluid in vivo, where shear stress within blood vessels pushes fluid into the interstitial space, which is subsequently transported to the nearby lymphatic capillaries. Results of our cell culture optimization study clearly show an increased vessel sprouting number, length, and morphological characteristics under dynamic cultivation conditions and physiological relevant mechanobiological stimulation. For the first time, a microvascular on-chip system incorporating microcapillaries of both blood and lymphatic origin in vitro recapitulates the interstitial blood-lymph interface.

Fluid-Structure Interaction Modelling Predicts That Strain Transfer Through Focal Attachments of Osteoblast Cells are the Primary Mediators of Mechanical Stimulation Under Fluid Flow

2013 ◽  
Author(s):  
T. J. Vaughan ◽  
M. G. Haugh ◽  
L. M. McNamara
Keyword(s):  
Fluid Flow ◽  
Mechanical Stimulation ◽  
Interstitial Fluid ◽  
Bone Cells ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Interaction Modelling

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. It has been proposed that indirect strain-induced flow of interstitial fluid surrounding bone cells may be the primary mediator of mechanical stimuli in-vivo [1]. Due to the practical difficulties in ascertaining whether interstitial fluid flow is indeed the primary mediator of mechanical stimuli in the in vivo environment, much of the evidence supporting this theory has been established through in vitro investigations that have observed cellular activity in response to fluid flow imposed by perfusion chambers [2]. While such in vitro experiments have identified key mechanisms involved in the mechanotransduction process, the exact mechanical stimulus being imparted to cells within a monolayer is unknown [3]. Furthermoreit is not clear whether the mechanical stimulation is comparable between different experimental systems or, more importantly, is representative of physiological loading conditions experienced by bone cells in vivo.

scholarly journals TAMI-15. THE EFFECT OF INTERSTITIAL FLUID FLOW AND ASTROCYTES / MICROGLIA ON INVASION, PROLIFERATION AND STEMNESS OF PATIENT-DERIVED GLIOMA STEM CELLS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii216-ii216
Author(s):  
Naciye Atay ◽  
Jessica Yuan ◽  
Chase Cornelison ◽  
Jennifer Munson
Keyword(s):  
Stem Cells ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Pressure Head ◽  
Molecular Classification ◽  
Patient Specific ◽  
Glioma Stem Cells ◽  
Interstitial Fluid Flow ◽  
Static Conditions

Abstract SIGNIFICANCE Glioblastoma is a highly infiltrative, malignant, and deadly glioma that can be classified into subtypes based on molecular classification. Treatment resistant glioma stem cells (GSCs) depend on the tumor microenvironment (TME) to drive recurrence. Cellular composition and interstitial fluid flow (IFF) are significant aspects of the TME. IFF and astrocyte and microglia (A+M) presence have independently been shown to mediate invasion. This study’s goal is to expand our knowledge of IFF and A+M effects on invasion to proliferation and stemness. METHODS Seven patient-derived GSC lines were tested in an in vitro 3D model, which consists of GSCs ± A+M resuspended in 0.2% hyaluronan / 0.12% rat tail collagen I gel. The gel was applied to an 8um pore 96-well transwell system. Flow and static conditions were modeled with and without a pressure head above the gel, respectively. Cells beyond the transwell membrane after 18 hrs of incubation were considered invaded. Stemness and proliferation were determined via flow cytometry for CD71 and Ki67, respectively. RESULTS/CONCLUSIONS The three mesenchymal GSC lines tested exhibited the largest IFF fold increases in stemness, proliferation, and invasion with averages of 23.9, 19.1, and 2.1, respectively. CD44+ cell populations, highest in mesenchymal cells, had a strong correlation with proliferation (R=0.8439) and stemness (R=0.7829) under flow. Furthermore, depending on the cell line/subtype, the addition of A+M either amplified, reduced, reversed, mitigated, or kept constant the effect of IFF on invasion and proliferation. Incorporating A+M never amplified the effect of IFF on stemness. Adding A+M had a strong effect on the IFF fold change of at least one parameter in six of the cell lines. This is the first presentation showing that IFF, patient-specific, and context-specific factors contribute to both increased proliferation, and maintenance of stem-like phenotypes in glioma.

Direct Hydraulic Permeability Measurements of Agarose Hydrogels Used as Cell Scaffolds

1999 ◽  
Author(s):  
Michael A. Soltz ◽  
Anna Stankiewicz ◽  
Gerard Ateshian ◽  
Robert L. Mauck ◽  
Clark T. Hung
Keyword(s):  
Fluid Flow ◽  
Articular Cartilage ◽  
Interstitial Fluid ◽  
Convective Transport ◽  
Hydraulic Permeability ◽  
Interstitial Fluid Flow ◽  
Pass Through ◽  
Fluid Pressurization ◽  
First Time

Abstract The objective of this study was to determine the intrinsic hydraulic permeability of 2% agarose hydrogels. Two-percent agarose was chosen because it is a concentration typically used for encapsulation of chondrocytes in suspension cultures [3–5], Hydraulic permeability is a measure of the relative ease by which fluid can pass through a material. Importantly, it governs the level of interstitial fluid flow as well as the interstitial fluid pressurization that is generated in a material during loading. Fluid pressurization is the source of the unique load-bearing and lubrication properties of articular cartilage [1,17] and represents a major component of the in vivo chondrocyte environment. We have previously reported that 2% agarose hydrogels can support fluid pressurization, albeit to a significantly lesser degree than articular cartilage [18]. Interstitial fluid flow gives rise to convective transport of nutrients and ions [6,7] and matrix compaction [9] which may serve as important stimuli to chondrocytes. We report for the first time the strain-dependent hydraulic permeability of 2% agarose hydrogels.

Transient interstitial fluid flow in brain tumors: Effect on drug delivery

2005 ◽  
Vol 60 (17) ◽  
pp. 4803-4821 ◽  
Author(s):  
Chee Seng Teo ◽  
Wilson Hor Keong Tan ◽  
Timothy Lee ◽  
Chi-Hwa Wang
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Brain Tumors ◽  
Interstitial Fluid ◽  
Interstitial Fluid Flow

scholarly journals Interstitial Fluid Flow and Transport in Glioblastoma and Surrounding Parenchyma in Patients

2020 ◽  
Author(s):  
Krishnashis Chatterjee ◽  
Naciye Atay ◽  
Daniel Abler ◽  
Saloni Bhargava ◽  
Prativa Sahoo ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Interstitial Fluid ◽  
Analysis Method ◽  
Interstitial Fluid Flow ◽  
Velocity Magnitude ◽  
Flow Pathways ◽  
Patient Prognosis ◽  
Models Of Disease ◽  
And Diffusion

Background: Glioblastoma is the deadliest, yet most common, brain tumor in adults, with poor survival and response to aggressive therapy. Therapeutic failure results from a number of causes inherent to these tumors. Imaging, computational, and drug delivery approaches can aid in the quest to access and kill each tumor cell in patients. One factor, interstitial fluid flow, is a driving force therapeutic delivery. However, convective and diffusive transport mechanisms are un-der-studied. In this study, we examine the application of a novel image analysis method to meas-ure fluid flow and diffusion in glioblastoma patients with MRI and compare to patient outcomes. Methods: Building on a prior imaging methodology tested and validated in vitro, in silico and in preclinical models of disease, here we apply our analysis method to archival patient data from the Ivy GAP dataset. Results: We characterize interstitial fluid flow and diffusion patterns in patients. We find strong correlations between flow rates measured within tumors and in the surrounding parenchymal space, where we hypothesized that velocities would be higher. Looking at overall magnitudes, there is significant correlation with both age and survival in this patient cohort. Additionally, we find that tumor size nor resection significantly alter the velocity magnitude. Last, we map the flow pathways in patient tumors and find variability in degree of directionality that we hypothesize in future studies may lead to information concerning treatment, invasive spread, and progression. Conclusions: Analysis of standard DCE-MRI in patients with glioblastoma offers more infor-mation regarding transport within and around tumor, can be measured post-resection and mag-nitudes correlate with patient prognosis.

scholarly journals Interstitial Fluid Flow: The Mechanical Environment of Cells and Foundation of Meridians

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Yao ◽  
Yabei Li ◽  
Guanghong Ding
Keyword(s):  
Numerical Simulation ◽  
Shear Stress ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Lower Limbs ◽  
Interstitial Tissue ◽  
Interstitial Fluid Flow ◽  
Mechanical Environment ◽  
Simulation Results

Using information from the deep dissection, microobservation, and measurement of acupoints in the upper and lower limbs of the human body, we developed a three-dimensional porous medium model to simulate the flow field using FLUENT software and to study the shear stress on the surface of interstitial cells (mast cells) caused by interstitial fluid flow. The numerical simulation results show the following: (i) the parallel nature of capillaries will lead to directional interstitial fluid flow, which may explain the long interstitial tissue channels or meridians observed in some experiments; (ii) when the distribution of capillaries is staggered, increases in the velocity alternate, and the velocity tends to be uniform, which is beneficial for substance exchange; (iii) interstitial fluid flow induces a shear stress, with magnitude of several Pa, on interstitial cell membranes, which will activate cells and lead to a biological response; (iv) capillary and interstitial parameters, such as capillary density, blood pressure, capillary permeability, interstitial pressure, and interstitial porosity, affect the shear stress on cell surfaces. The numerical simulation results suggest that in vivo interstitial fluid flow constitutes the mechanical environment of cells and plays a key role in guiding cell activities, which may explain the meridian phenomena and the acupuncture effects observed in experiments.

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