Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro

2005 ◽  
Vol 118 (20) ◽  
pp. 4731-4739 ◽  
Author(s):  
C. P. Ng
Keyword(s):  
Fluid Flow ◽  
Interstitial Fluid ◽  
Myofibroblast Differentiation ◽  
Interstitial Fluid Flow ◽  
Collagen Alignment

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.

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.

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.

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 A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment

2020 ◽  
Author(s):  
R. C. Cornelison ◽  
J. X. Yuan ◽  
K. M. Tate ◽  
A. Petrosky ◽  
G. F. Beeghly ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Interstitial Fluid ◽  
Tumor Model ◽  
Drug Efficacy ◽  
Interstitial Fluid Flow ◽  
Diffuse Infiltration ◽  
Human Astrocytes ◽  
Resected Patient ◽  
The Brain

AbstractGlioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We recreate this infiltrative microenvironment in vitro based on resected patient tumors and examine malignancy metrics (invasion, proliferation, and stemness) in the context of cellular and biophysical factors and therapies. Our 3D tissue-engineered model comprises patient-derived glioma stem cells, human astrocytes and microglia, and interstitial fluid flow. We found flow contributes to all outcomes across seven patient-derived lines, and glial effects are driven by CCL2 and differential glial activation. We conducted a six-drug screen using four outcomes and find expression of putative stemness marker CD71, opposed to viability IC50, significantly predicts murine xenograft survival. Our results dispute the paradigm of viability as predictive of drug efficacy. We posit this patient-centric, infiltrative tumor model is a novel advance towards translational personalized medicine.

scholarly journals On the characterization of interstitial fluid flow in the skeletal muscle endomysium

2020 ◽  
Vol 102 ◽  
pp. 103504 ◽  
Author(s):  
Qiuyun Wang ◽  
Shaopeng Pei ◽  
X. Lucas Lu ◽  
Liyun Wang ◽  
Qianhong Wu
Keyword(s):  
Skeletal Muscle ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Interstitial Fluid Flow

scholarly journals Interstitial flow promotes macrophage polarization toward an M2 phenotype

2018 ◽  
Vol 29 (16) ◽  
pp. 1927-1940 ◽  
Author(s):  
Ran Li ◽  
Jean Carlos Serrano ◽  
Hao Xing ◽  
Tara A. Lee ◽  
Hesham Azizgolshani ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cell ◽  
Interstitial Fluid ◽  
Macrophage Polarization ◽  
Interstitial Flow ◽  
Interstitial Fluid Flow ◽  
M2 Polarization ◽  
Tumor Tissues

Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment.

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