Engineering the Lymphatic System

Nipper, Matthew E.; Dixon, J. Brandon

doi:10.1007/s13239-011-0054-6

Cited by 39 publications

(36 citation statements)

References 97 publications

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“…It is commonly supposed that variations in lymphatic pressure play a significant role in interstitial drainage [15,37,39,40,55,57]. The size of such variations is typically around 100 Pa which compares to a mean pressure difference between blood and lymphatic capillaries of around 3000 Pa. At the end of §2 we noted that the steady state solution to the model depends only on lymphatic pressure P l and blood capillary pressure P b through their difference P b − P l .…”

Section: Discussionmentioning

confidence: 77%

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve

2015

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This study investigates fluid flow and elastic deformation in tissues that are drained by the primary lymphatic system. A model is formulated based on the Rossi hypothesis that states that the primary lymphatic valves, which are formed by overlapping endothelial cells around the circumferential lining of lymphatic capillaries, open in response to swelling of the surrounding tissue. Tissue deformation and interstitial fluid flow through the tissue are treated using the Biot equations of poroelasticity and, the fluid flux, (into the interstitium) across the walls of the blood capillaries, is assumed to be linearly related to the pressure difference across the walls via a constant of proportionality (the vascular permeability). The resulting model is solved in a periodic domain containing one blood capillary and one lymphatic capillary starting from a configuration in which the tissue is undeformed. On imposition of a constant pressure difference between blood and lymphatic capillaries the solutions are found to settle to a steady state. Given that the magnitude of pressure fluctuations in the lymphatic system is much smaller than this pressure difference between blood and lymph it is postulated that the resulting steady state solution gives a good representation of the state of the tissue under physiological conditions. The effects of changes to the Young's modulus of the tissue, the blood-lymphatic pressure difference, vascular permeability and valve dimensions on the steady state are investigated and discussed in terms of their effects on oedema in the context of age-and pregnancy-related changes to the body.

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Section: Discussionmentioning

confidence: 77%

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve

2015

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“…Collecting lymphatic ducts possess unidirectional valves and contractile vascular smooth muscle cells that promote egress of interstitial fluid towards regional lymph node basins. Shear stresses within initial or immature lymphatics are estimated to be <0.2–1 dyne cm 2 , whereas transport downstream in larger collecting vessels is pulsatile and can reach maximal intensities of 5 dyne cm −2 at the vessel wall1819. To evaluate specifically the effects of fluid force on cancer cells, we microengineered a biomimetic platform to model mechanical properties and predictions of fluid movement across tumour cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Fluid shear stress activates YAP1 to promote cancer cell motility

et al. 2017

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Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1–TEAD interaction reduces cellular velocity to levels observed without flow. Silencing of TEAD phenocopies loss of YAP1, implicating transcriptional transactivation function in mediating force-enhanced cell migration. WSS dictates expression of a network of YAP1 effectors with executive roles in invasion, chemotaxis and adhesion downstream of the ROCK–LIMK–cofilin signalling axis. Altogether, these data implicate YAP1 as a fluid mechanosensor that functions to regulate genes that promote metastasis.

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“…This active pumping is crucial in lymphatic transport because interstitial fluid pressure alone is insufficient to move lymph against the adverse pressure gradient inherent to the system [2]. To aid in transferring this bulk of fluid, which recent estimates put at almost 8 liters per day for humans [25], the collecting lymphatics are separated into unit segments termed lymphangions [41, 29] by one-way valves. These anatomical structures are similar to those found in veins and help ensure unidirectional flow of lymph towards its exit at the left subclevian vein.…”

Section: Introductionmentioning

confidence: 99%

Ex Vivo Lymphatic Perfusion System for Independently Controlling Pressure Gradient and Transmural Pressure in Isolated Vessels

Kornuta

Dixon

2014

Ann Biomed Eng

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In addition to external forces, collecting lymphatic vessels intrinsically contract to transport lymph from the extremities to the venous circulation. As a result, the lymphatic endothelium is routinely exposed to a wide range of dynamic mechanical forces, primarily fluid shear stress and circumferential stress, which have both been shown to affect lymphatic pumping activity. Although various ex-vivo perfusion systems exist to study this innate pumping activity in response to mechanical stimuli, none are capable of independently controlling the two primary mechanical forces affecting lymphatic contractility: transaxial pressure gradient, ΔP, which governs fluid shear stress; and average transmural pressure, Pavg, which governs circumferential stress. Hence, the authors describe a novel ex-vivo lymphatic perfusion system (ELPS) capable of independently controlling these two outputs using a linear, explicit model predictive control (MPC) algorithm. The ELPS is capable of reproducing arbitrary waveforms within the frequency range observed in the lymphatics in vivo, including a time-varying ΔP with a constant Pavg, time-varying ΔP and Pavg, and a constant ΔP with a time-varying Pavg. In addition, due to its implementation of syringes to actuate the working fluid, a post-hoc method of estimating both the flow rate through the vessel and fluid wall shear stress over multiple, long (5 sec) time windows is also described.

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Engineering the Lymphatic System

Cited by 39 publications

References 97 publications

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve

Fluid shear stress activates YAP1 to promote cancer cell motility

Ex Vivo Lymphatic Perfusion System for Independently Controlling Pressure Gradient and Transmural Pressure in Isolated Vessels

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