scholarly journals Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis

2021 ◽  
Author(s):  
Lingzhi Jing ◽  
Suna Fan ◽  
Xiang Yao ◽  
Yaopeng Zhang
Keyword(s):  
Cell Proliferation ◽  
Shear Stress ◽  
Stem Cell ◽  
Fluid Shear Stress ◽  
Culture Conditions ◽  
Fluid Shear ◽  
Ultrasound Stimulation ◽  
Orthopedic Diseases ◽  
Stimulation Of

Abstract Bone tissue with strong adaptability is often in a complex dynamical microenvironment in vivo, which is associated with the pathogenesis and treatment of orthopedic diseases. Therefore, it is of great significance to investigate the effects of corresponding compound stimulation on cell behaviors. Herein, a fluid shear stress (FSS) plus ultrasound stimulation platform suitable for cell studies based on a microfluidic chip was constructed and bone marrow mesenchymal stem cell (BMSC) was chosen as a model cell. The proliferation and osteogenesis of BMSCs under the compound stimulation of FSS plus ultrasound in growth medium without any soluble induction factors were firstly investigated. Single FSS stimulation and static culture conditions were also examined. Results illustrated that suitable single FSS stimulation (about 0.06 dyn/cm2) could significantly enhance cell proliferation and osteogenesis simultaneously when compare to the static control, while greater FSS mitigated or even restricted these enhancing effects. Interestingly, ultrasound stimulation combined with this suitable FSS stimulation further accelerated cell proliferation as the intensity of ultrasound increasing. As for the osteogenesis under compound stimulation, it was relatively restricted under lower ultrasound intensity (about 0.075 W/cm2), while promoted when the intensity became higher (about 1.75W/cm2). This study suggests that both the cell proliferation and osteogenesis are very responsive to the magnitudes of FSS and ultrasound stimulations and can be both significantly enhanced by proper combination strategies. Moreover, these findings will provide valuable references for the construction of effective cell bioreactors and also the treatment of orthopedic diseases.

Device-Based In Vitro Techniques for Mechanical Stimulation of Vascular Cells: A Review

2015 ◽  
Vol 137 (4) ◽  
Author(s):  
Caleb A. Davis ◽  
Steve Zambrano ◽  
Pratima Anumolu ◽  
Alicia C. B. Allen ◽  
Leonardo Sonoqui ◽  
...  
Keyword(s):  
Shear Stress ◽  
Mechanical Stimulation ◽  
Fluid Shear Stress ◽  
Vascular Cells ◽  
Fluid Shear ◽  
Advantages And Disadvantages ◽  
Applied Forces ◽  
Stimulation Of

The most common cause of death in the developed world is cardiovascular disease. For decades, this has provided a powerful motivation to study the effects of mechanical forces on vascular cells in a controlled setting, since these cells have been implicated in the development of disease. Early efforts in the 1970 s included the first use of a parallel-plate flow system to apply shear stress to endothelial cells (ECs) and the development of uniaxial substrate stretching techniques (Krueger et al., 1971, “An in Vitro Study of Flow Response by Cells,” J. Biomech., 4(1), pp. 31–36 and Meikle et al., 1979, “Rabbit Cranial Sutures in Vitro: A New Experimental Model for Studying the Response of Fibrous Joints to Mechanical Stress,” Calcif. Tissue Int., 28(2), pp. 13–144). Since then, a multitude of in vitro devices have been designed and developed for mechanical stimulation of vascular cells and tissues in an effort to better understand their response to in vivo physiologic mechanical conditions. This article reviews the functional attributes of mechanical bioreactors developed in the 21st century, including their major advantages and disadvantages. Each of these systems has been categorized in terms of their primary loading modality: fluid shear stress (FSS), substrate distention, combined distention and fluid shear, or other applied forces. The goal of this article is to provide researchers with a survey of useful methodologies that can be adapted to studies in this area, and to clarify future possibilities for improved research methods.

scholarly journals Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway

2017 ◽  
Vol 28 (19) ◽  
pp. 2508-2517 ◽  
Author(s):  
Kimberly R. Long ◽  
Katherine E. Shipman ◽  
Youssef Rbaibi ◽  
Elizabeth V. Menshikova ◽  
Vladimir B. Ritov ◽  
...  
Keyword(s):  
Shear Stress ◽  
Ion Transport ◽  
Proximal Tubule ◽  
Fluid Shear Stress ◽  
Kidney Development ◽  
Endocytic Pathway ◽  
Fluid Shear ◽  
Intermediate Phenotypes ◽  
Glomerulotubular Balance

Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain the high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate ion transport in response to changes in glomerular filtration rate (GFR) to maintain glomerulotubular balance. PT cells in culture up-regulate endocytic capacity in response to acute changes in fluid shear stress (FSS); however, it is not known whether GFR modulates PT endocytosis to enable maximally efficient uptake of filtered proteins in vivo. Here, we show that cells cultured under continuous FSS develop an expanded apical endocytic pathway and increased endocytic capacity and lysosomal biogenesis. Furthermore, endocytic capacity in fully differentiated cells is rapidly modulated by changes in FSS. PT cells exposed to continuous FSS also acquired an extensive brush border and basolateral membrane invaginations resembling those observed in vivo. Culture under suboptimal levels of FSS led to intermediate phenotypes, suggesting a threshold effect. Cells exposed to FSS expressed higher levels of key proteins necessary for PT function, including ion transporters, receptors, and membrane-trafficking machinery, and increased adenine nucleotide levels. Inhibition of the mechanistic target of rapamycin (mTOR) using rapamycin prevented the increase in cellular energy levels, lysosomal biogenesis, and endocytic uptake, suggesting that these represent a coordinated differentiation program. In contrast, rapamycin did not prevent the FSS-induced increase in Na+/K+-ATPase levels. Our data suggest that rapid tuning of the endocytic response by changes in FSS may contribute to glomerulotubular balance in vivo. Moreover, FSS provides an essential stimulus in the differentiation of PT cells via separate pathways that up-regulate endocytosis and ion transport capacity. Variations in FSS may also contribute to the maturation of PT cells during kidney development and during repair after kidney injury.

scholarly journals ShearFAST: a user-friendly in vitro toolset for high throughput, inexpensive fluid shear stress experiments.

2020 ◽  
Author(s):  
Thomas Brendan Smith ◽  
Alessandro Marco De Nunzio ◽  
Kamlesh Patel ◽  
Haydn Munford ◽  
Tabeer Alam ◽  
...  
Keyword(s):  
Shear Stress ◽  
High Throughput ◽  
Fluid Shear Stress ◽  
Tracking System ◽  
Frequency Measurement ◽  
Camera Motion ◽  
Fluid Shear ◽  
Mean Frequency

Fluid shear stress is a key modulator of cellular physiology in vitro and in vivo, but its effects are under-investigated due to requirements for complicated induction methods. Herein we report the validation of ShearFAST; a smartphone application that measures the rocking profile on a standard laboratory cell rocker and calculates the resulting shear stress arising in tissue culture plates. The accuracy with which this novel approach measured rocking profiles was validated against a graphical analysis, and also against measures reported by an 8-camera motion tracking system. ShearFASTs angle assessments correlated well with both analyses (r ≥0.99, p ≤0.001) with no significant differences in pitch detected across the range of rocking angles tested. Rocking frequency assessment by ShearFAST also correlated well when compared to the two independent validatory techniques (r ≥0.99, p ≤0.0001), with excellent reproducibility between ShearFAST and video analysis (mean frequency measurement difference of 0.006 ± 0.005Hz) and motion capture analysis (mean frequency measurement difference of 0.008 ± 0.012Hz). These data make the ShearFAST assisted cell rocker model make it an attractive approach for economical, high throughput fluid shear stress experiments. Proof of concept data presented reveals a protective effect of low-level shear stress on renal proximal tubule cells submitted to simulations of pretransplant storage.

Nanoparticle localization in blood vessels: dependence on fluid shear stress, flow disturbances, and flow-induced changes in endothelial physiology

Nanoscale ◽  
2018 ◽  
Vol 10 (32) ◽  
pp. 15249-15261 ◽  
Author(s):  
M. Juliana Gomez-Garcia ◽  
Amber L. Doiron ◽  
Robyn R. M. Steele ◽  
Hagar I. Labouta ◽  
Bahareh Vafadar ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Fluid Shear ◽  
Nanoparticle Distribution ◽  
Flow Models ◽  
Flow Disturbances ◽  
Induced Changes ◽  
Stress Flow

Hemodynamic factors drive nanoparticle distribution in vivo and in vitro in cell-based flow models.

scholarly journals CD44 regulates blood-brain barrier integrity in response to fluid shear stress

2020 ◽  
Author(s):  
Brandon J. DeOre ◽  
Paul P. Partyka ◽  
Fan Fan ◽  
Peter A. Galie
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Blood Brain Barrier ◽  
Fluid Shear Stress ◽  
Small Gtpase ◽  
Brain Barrier ◽  
Fluid Shear ◽  
Blood Brain

AbstractFluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the response of the blood-brain barrier to shear have yet to be studied in cerebral vasculature despite its importance for brain homeostasis. The goal of this study is to probe components of shear mechanotransduction within the blood-brain barrier to gain a better understanding of pathologies associated with changes in cerebral blood flow including ischemic stroke. Interrogating the effects of shear stress in vivo is complicated by the complexity of factors in the brain parenchyma and the difficulty associated with modulating blood flow regimes. Recent advances in the ability to mimic the in vivo microenvironment using three-dimensional in vitro models provide a controlled setting to study the response of the blood-brain barrier to shear stress. The in vitro model used in this study is compatible with real-time measurement of barrier function using transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level of shear stress required for barrier formation and that the composition of the extracellular matrix, specifically the presence of hyaluronan, dictates the flow response. Gene editing to modulate the expression of CD44, a receptor for hyaluronan that previous studies have identified to be mechanosensitive, demonstrates that the receptor is required for the endothelial response to shear stress. Manipulation of small GTPase activity reveals CD44 activates Rac1 while inhibiting RhoA activation. Additionally, adducin-γ localizes to tight junctions in response to shear stress and RhoA inhibition and is required to maintain the barrier. This study identifies specific components of the mechanosensing complex associated with the blood-brain barrier response to fluid shear stress, and therefore illuminates potential targets for barrier manipulation in vivo.

scholarly journals PGC1α Regulates the Endothelial Response to Fluid Shear Stress via Telomerase Reverse Transcriptase Control of Heme Oxygenase-1

2021 ◽  
Author(s):  
Shashi Kant ◽  
Khanh-Van Tran ◽  
Miroslava Kvandova ◽  
Amada D. Caliz ◽  
Hyung-Jin Yoo ◽  
...  
Keyword(s):  
Shear Stress ◽  
Reverse Transcriptase ◽  
Heme Oxygenase ◽  
Fluid Shear Stress ◽  
Heme Oxygenase 1 ◽  
Telomerase Reverse Transcriptase ◽  
Fluid Shear ◽  
Flow Alignment

Fluid shear stress (FSS) is known to mediate multiple phenotypic changes in the endothelium. Laminar FSS (undisturbed flow) is known to promote endothelial alignment to flow that is key to stabilizing the endothelium and rendering it resistant to atherosclerosis and thrombosis. The molecular pathways responsible for endothelial responses to FSS are only partially understood. Here we have identified peroxisome proliferator gamma coactivator-1α (PGC-1α) as a flow-responsive gene required for endothelial flow alignment in vitro and in vivo. Compared to oscillatory FSS (disturbed flow) or static conditions, laminar FSS (undisturbed flow) increased PGC-1α expression and its transcriptional co-activation. PGC-1α was required for laminar FSS-induced expression of telomerase reverse transcriptase (TERT) in vitro and in vivo via its association with ERRα and KLF4 on the TERT promoter. We found that TERT inhibition attenuated endothelial flow alignment, elongation, and nuclear polarization in response to laminar FSS in vitro and in vivo. Among the flow-responsive genes sensitive to TERT status was heme oxygenase-1 (HMOX1), a gene required for endothelial alignment to laminar FSS. Thus, these data suggest an important role for a PGC-1α-TERT-HMOX1 axis in the endothelial stabilization response to laminar FSS.

Differential Responses of Endothelial Cells to Positive and Negative Wall Shear Stress Gradients

2010 ◽  
Author(s):  
Jennifer Dolan ◽  
Sukhjinder Singh ◽  
Hui Meng ◽  
John Kolega
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Vessel Wall ◽  
Fluid Shear Stress ◽  
Cerebral Aneurysms ◽  
In Vivo Studies ◽  
Outer Side ◽  
Fluid Shear ◽  
Wall Shear

Cerebral aneurysms tend to develop at bifurcation apices or the outer side of curved vessels where the blood vessel wall experiences complex hemodynamics. In vivo studies have recently revealed that the initiation of cerebral aneurysms is confined to a well-defined hemodynamic microenvironment. Specifically aneurysms form where the vessel wall experiences high fluid shear stress (wall shear stress, WSS) and flow is accelerating, so that the wall is exposed to a positive spatial gradient in the fluid shear stress (wall shear stress gradient, WSSG)[1,2]. Closer examination of such in vivo studies reveals that exposure of the vessel wall to equally high WSS in the presence of decelerating flow, that is, negative WSSG, does not result in aneurysm-like remodeling.

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