Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro

Ng, Chee Ping; Helm, Cara-Lynn E.; Swartz, Melody A.

doi:10.1016/j.mvr.2004.08.002

Cited by 188 publications

(186 citation statements)

References 21 publications

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“…As example applications of our system, we verified that interstitial flow stimulates LECs and BECs to form multicellular structures with lumen, and furthermore that flow synergizes with matrix-bound VEGF to drive more robust capillary formation as previously demonstrated in more cumbersome, single-chamber systems (Helm et al, 2005;Ng et al, 2004). Indeed, our device has many features which could prove useful to those studying angiogenesis and lymphangiogenesis, as the effects of different growth factors or inhibitors on cell morphogenesis and structure formation can be compared, as well as synergistic effects between flow and signaling molecules, which we demonstrated here (Fig.…”

Section: Discussionsupporting

confidence: 77%

“…Since all chambers shared the same reservoirs, the fluid pressure drop across each is the same, leading to a similar flow velocity in each case providing that the resistance is the same in each gel (since velocity is inversely related to K 0 ). The nine-chamber radial flow system was based on a previously developed radial flow chamber Swartz, 2003, 2006;Ng et al, 2004Ng et al, , 2005. Nine smaller versions of the single chamber fit onto a system with a total diameter of 5 cm, which can be placed in a traditional Petri dish and mounted on a microscope stage, and each chamber holds 40 mL, significantly reducing the amount of reagents and the number of cells used.…”

Section: Resultsmentioning

confidence: 99%

“…We compared static versus flow conditions on LECs, as flow was previously shown to promote lymphatic capillarogenesis (Boardman and Swartz, 2003;Ng et al, 2004), as well as the effects of matrix-bound VEGF on LEC and BEC morphogenesis under flow (Helm et al, 2005) for 10 days. We found that interstitial flow of 1-2 mm/s induced from a 5 mm pressure drop (Fig.…”

Section: Capillary Morphogenesis Under Flow and A 2 Pi 1-8 -Vegf 121mentioning

confidence: 99%

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A multichamber fluidic device for 3D cultures under interstitial flow with live imaging: Development, characterization, and applications

Bonvin

Overney

Shieh

et al. 2010

Biotech & Bioengineering

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Interstitial flow is an important biophysical cue that can affect capillary morphogenesis, tumor cell migration, and fibroblast remodeling of the extracellular matrix, among others. Current models that incorporate interstitial flow and that are suitable for live imaging lack the ability to perform multiple simultaneous experiments, for example, to compare effects of growth factors, extracellular matrix composition, etc. We present a nine-chamber radial flow device that allows simultaneous 3D fluidic experiments for relatively long-term culture with live imaging capabilities. Flow velocity profiles were characterized by fluorescence recovery after photobleaching (FRAP) for flow uniformity and estimating the hydraulic conductivity. We demonstrate lymphatic and blood capillary morphogenesis in fibrin gels over 10 days, comparing flow with static conditions as well as the effects of an engineered variant of VEGF that binds fibrin via Factor XIII. We also demonstrate the culture of contractile fibroblasts and co-cultures with tumor cells for modeling the tumor microenvironment. Therefore, this device is useful for studies of capillary morphogenesis, cell migration, contractile cells like fibroblasts, and multicellular cultures, all under interstitial flow. Biotechnol. Bioeng. 2010;105: 982-991.

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Section: Discussionsupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Capillary Morphogenesis Under Flow and A 2 Pi 1-8 -Vegf 121mentioning

confidence: 99%

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A multichamber fluidic device for 3D cultures under interstitial flow with live imaging: Development, characterization, and applications

Bonvin

Overney

Shieh

et al. 2010

Biotech & Bioengineering

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“…In addition to regulating function, fluid flow is also an important regulator of lymphatic morphogenesis or lymphangiogenesis, and has been shown to drive lymphatic capillary organization in dermal wound healing models [45,46] as well as in vitro culture models [47][48][49]. Without flow, as in the case of lymphedema, lymphatic endothelium becomes hyperplastic (i.e.…”

Section: Lymphatic Physiology and Neogenesismentioning

confidence: 99%

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Lund

Swartz

2010

J Mammary Gland Biol Neoplasia

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Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

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“…While normal IF can be in the range of 0.1-1 mm/s (Chary and Jain, 1989;Dafni et al, 2002), increased IF in such inflammatory environments are evidenced by drastically increased lymph flow rates (Mullins and Hudgens, 1987;Matsumoto et al, 1990;He et al, 2002;Modi et al, 2007) because lymph drains the interstitial space. In addition to its role in wound healing, IF is important for tissue homeostasis via transport of metabolites and cell-signaling molecules; it is also an important morphoregulator both in vivo (Boardman and Swartz, 2003;Hirokawa et al, 2006;Schweickert et al, 2007) and in vitro, where it has been used to engineer functional blood and lymphatic capillaries (Ng et al, 2004;Helm et al, 2005;Semino et al, 2006;Helm et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Cells in 3D matrices under interstitial flow: Effects of extracellular matrix alignment on cell shear stress and drag forces

Pedersen

Lichter

Swartz

2010

Journal of Biomechanics

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a b s t r a c tInterstitial flow is an important regulator of various cell behaviors both in vitro and in vivo, yet the forces that fluid flow imposes on cells embedded in a 3D extracellular matrix (ECM), and the effects of matrix architecture on those forces, are not well understood. Here, we demonstrate how fiber alignment can affect the shear and pressure forces on the cell and ECM. Using computational fluid dynamics simulations, we show that while the solutions of the Brinkman equation accurately estimate the average fluid shear stress and the drag forces on a cell within a 3D fibrous medium, the distribution of shear stress on the cellular surface as well as the peak shear stresses remain intimately related to the pericellular fiber architecture and cannot be estimated using bulk-averaged properties. We demonstrate that perpendicular fiber alignment of the ECM yields lower shear stress and pressure forces on the cells and higher stresses on the ECM, leading to decreased permeability, while parallel fiber alignment leads to higher stresses on cells and increased permeability, as compared to a cubic lattice arrangement. The Spielman-Goren permeability relationships for fibrous media agreed well with CFD simulations of flow with explicitly considered fibers. These results suggest that the experimentally observed active remodeling of ECM fibers by fibroblasts under interstitial flow to a perpendicular alignment could serve to decrease the shear and drag forces on the cell.

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Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro

Cited by 188 publications

References 21 publications

A multichamber fluidic device for 3D cultures under interstitial flow with live imaging: Development, characterization, and applications

A multichamber fluidic device for 3D cultures under interstitial flow with live imaging: Development, characterization, and applications

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Cells in 3D matrices under interstitial flow: Effects of extracellular matrix alignment on cell shear stress and drag forces

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