Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell–Cell Interactions

Chung, Seok; Sudo, Ryo; Vickerman, Vernella; Zervantonakis, Ioannis K.; Kamm, Roger D.

doi:10.1007/s10439-010-9899-3

Cited by 144 publications

(132 citation statements)

References 96 publications

(114 reference statements)

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“…Microfluidic technology has several advantages over conventional methods in terms of precise control of microenvironmental factors, and high-resolution imaging of cell motility or cell-to-cell interactions. 12,13 Several studies have utilized microfluidic technology to model different stages of the cancer metastasis. Kim et al have reported a cancer angiogenesis model by attaching endothelial cells on the sidewall of fibrin gel, and stimulating them by co-culturing with spatially separated cancer cells.…”

Section: B)mentioning

confidence: 99%

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

et al. 2014

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Understanding the mechanism behind cancer metastasis is a major challenge in cancer biology. Several in vitro models have been developed to mimic a cancer microenvironment by engineering cancer-endothelial cell (EC) and cancer-stromal cell interactions. It has been challenging to realistically mimic angiogenesis, intravasation, and extravasation using macro-scale approaches but recent progress in microfluidics technology has begun to yield promising results. We present a metastasis chip that produce microvessels, where EC and stromal cells can be patterned in close proximity to tumor cells. The vessels are formed following a natural morphogenic process and have smooth boundaries with proper cell-cell junctions. The engineered microvessels are perfusable and have well-defined openings toward inlet and outlet channels. The ability to introduce cancer cells into different locations bordering to the microvessel wall allowed generation and maintenance of appropriate spatial gradients of growth factors and attractants. Cancer angiogenesis and its inhibition by anti-vascular endothelial growth factor (bevacizumab) treatment were successfully reproduced in the metastasis chip. Cancer intravasation and its modulation by treatment of tumor necrosis factor-a were also modeled. Compared to other models, the unique design of the metastasis chip that engineers a clear EC-cancer interface allows precise imaging and quantification of angiogenic response as well as tumor cell trans-endothelial migration. The metastasis chip presented here has potential applications in the investigation of fundamental cancer biology as well as in drug screening. V C 2014 AIP Publishing LLC.

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Section: B)mentioning

confidence: 99%

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

et al. 2014

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“…Recently, cell migration on gradient materials [9] and their potential applications in tissue regeneration [10,11] have attracted more and more attention.…”

Section: Introductionmentioning

confidence: 99%

Gradient biomaterials and their influences on cell migration

et al. 2012

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Cell migration participates in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. The cells specifically migrate to destiny sites induced by the gradually varying concentration (gradient) of soluble signal factors and the ligands bound with the extracellular matrix in the body during a wound healing process. Therefore, regulation of the cell migration behaviours is of paramount importance in regenerative medicine. One important way is to create a microenvironment that mimics the in vivo cellular and tissue complexity by incorporating physical, chemical and biological signal gradients into engineered biomaterials. In this review, the gradients existing in vivo and their influences on cell migration are briefly described. Recent developments in the fabrication of gradient biomaterials for controlling cellular behaviours, especially the cell migration, are summarized, highlighting the importance of the intrinsic driving mechanism for tissue regeneration and the design principle of complicated and advanced tissue regenerative materials. The potential uses of the gradient biomaterials in regenerative medicine are introduced. The current and future trends in gradient biomaterials and programmed cell migration in terms of the long-term goals of tissue regeneration are prospected.

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“…7,8 For example, endothelial cells (ECs) have been seeded in fabricated microchannels on both nonbiological 9,10 substrates or within biological substrates 11,12 to mimic vessels; however, while this approach offers some insight into the effects of convective forces on cells, the channels are not living vessels and thus are unresponsive to the dynamic metabolic demands of the surrounding environment.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Perfused Human Capillary Networks

Moya

Hsu

Lee

et al. 2013

Tissue Engineering Part C: Methods

361

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Replicating in vitro the complex in vivo tissue microenvironment has the potential to transform our approach to medicine and also our understanding of biology. In order to accurately model the 3D arrangement and interaction of cells and extracellular matrix, new microphysiological systems must include a vascular supply. The vasculature not only provides the necessary convective transport of oxygen, nutrients, and waste in 3D culture, but also couples and integrates the responses of organ systems. Here we combine tissue engineering and microfluidic technology to create an in vitro 3D metabolically active stroma (*1 mm 3 ) that, for the first time, contains a perfused, living, dynamic, interconnected human capillary network. The range of flow rate (mm/s) and shear rate (s -1 ) within the network was 0-4000 and 0-1000, respectively, and thus included the normal physiological range. Infusion of FITC dextran demonstrated microvessels (15-50 mm) to be largely impermeable to 70 kDa. Our high-throughput biology-directed platform has the potential to impact a broad range of fields that intersect with the microcirculation, including tumor metastasis, drug discovery, vascular disease, and environmental chemical toxicity.

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Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell–Cell Interactions

Cited by 144 publications

References 96 publications

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

Gradient biomaterials and their influences on cell migration

In Vitro Perfused Human Capillary Networks

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