Tissue culture on a chip: Developmental biology applications of self‐organized capillary networks in microfluidic devices

Miura, Takashi; Yokokawa, Ryuji

doi:10.1111/dgd.12292

Cited by 18 publications

(11 citation statements)

References 101 publications

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“…Methods to create artificial vascular plexuses have been extensively studied in the field of bioengineering ( Miura and Yokokawa, 2016 ). These methods may be classified into two categories: predesigned method and self-organizing method ( Hasan et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling for meshwork formation of endothelial cells in fibrin gels

Sasaki

Nakajima

Yamaguchi

et al. 2017

Journal of Theoretical Biology

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Vasculogenesis is the earliest process in development for spontaneous formation of a primitive capillary network from endothelial progenitor cells. When human umbilical vein endothelial cells (HUVECs) are cultured on Matrigel, they spontaneously form a network structure which is widely used as an in vitro model of vasculogenesis. Previous studies indicated that chemotaxis or gel deformation was involved in spontaneous pattern formation. In our study, we analyzed the mechanism of vascular pattern formation using a different system, meshwork formation by HUVECs embedded in fibrin gels. Unlike the others, this experimental system resulted in a perfusable endothelial network in vitro. We quantitatively observed the dynamics of endothelial cell protrusion and developed a mathematical model for one-dimensional dynamics. We then extended the one-dimensional model to two-dimensions. The model showed that random searching by endothelial cells was sufficient to generate the observed network structure in fibrin gels.

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Section: Introductionmentioning

confidence: 99%

Mathematical modeling for meshwork formation of endothelial cells in fibrin gels

Sasaki

Nakajima

Yamaguchi

et al. 2017

Journal of Theoretical Biology

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“…There are two major vessel bioengineering methods, which include the "pre-designed method", where a hollow structure for the vascular network is prefabricated and the "self-organizing method", which relies on spontaneous formation of endothelial cells in tubes as occurs with vasculogenesis or angiogenesis (Miura and Yokokawa, 2016). Prefabrication requires seeding of endothelial cells in extracellular matrix (ECM) or polymer materials using photolithography ( Galie et al, 2014 ;Song et al, 2012 ;Song and Munn, 2011 ), needles ( Chrobak et al, 2006 ;Sadr et al, 2011 ;Usuba et al, 2019 ;Yoshida et al, 2013 ) or sacrifi cial molding ( Golden and Tien, 2007 ;Miller et al, 2012 ).…”

Section: Vascular Systemmentioning

confidence: 99%

Microphysiological systems in early stage drug development: Perspectives on current applications and future impact

et al. 2021

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Microphysiological systems (MPS) are making advances to provide more standardized and predictive physiologically relevant responses to test articles in living tissues and organ systems. The excitement surrounding the potential of MPS to better predict human responses to medicines and improving clinical translation is overshadowed by their relatively slow adoption by the pharmaceutical industry and regulators. Collaboration between multiorganizational consortia and regulators is necessary to build an understanding of the strengths and limitations of MPS models and closing the current gaps. Here, we review some of the advances in MPS research, focusing on liver, intestine, vascular system, kidney and lung and present examples highlighting the context of use for these systems. For MPS to gain a foothold in drug development, they must have added value over existing approaches. Ideally, the application of MPS will augment in vivo studies and reduce the use of animals via tiered screening with less reliance on exploratory toxicology studies to screen compounds. Because MPS support multiple cell types (e.g. primary or stem-cell derived cells) and organ systems, identifying when MPS are more appropriate than simple 2D in vitro models for understanding physiological responses to test articles is necessary. Once identified, MPS models require qualification for that specific context of use and must be reproducible to allow future validation. Ultimately, the challenges of balancing complexity with reproducibility will inform the promise of advancing the MPS field and are critical for realization of the goal to reduce, refine and replace (3Rs) the use of animals in nonclinical research.

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“…A technical obstacle for standard culture systems of three-dimensional tissue structures is the lack of microcirculation. There are various methods to improve oxygen supply, such as culture inserts and rotator culture [ 6 ]. However, these methods cannot overcome the size limitation, i.e., if the cultured tissue size exceeds a 100-μm order, the tissue undergoes necrosis due to hypoxia [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Predesigned methods align endothelial cells by engineering techniques. Self-organization methods employ the spontaneous pattern formation capacity of cells to generate capillary network structures (reviewed in [ 6 ]). Recent advances in the integrative studies of tissue engineering and vascular biology have enabled construction of a perfusable vascular network in vitro.…”

Section: Introductionmentioning

confidence: 99%

A new perfusion culture method with a self-organized capillary network

et al. 2020

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A lack of perfusion has been one of the most significant obstacles for three-dimensional culture systems of organoids and embryonic tissues. Here, we developed a simple and reliable method to implement a perfusable capillary network in vitro. The method employed the self-organization of endothelial cells to generate a capillary network and a static pressure difference for culture medium circulation, which can be easily introduced to standard biological laboratories and enables long-term cultivation of vascular structures. Using this culture system, we perfused the lumen of the self-organized capillary network and observed a flow-induced vascular remodeling process, cell shape changes, and collective cell migration. We also observed an increase in cell proliferation around the self-organized vasculature induced by flow, indicating functional perfusion of the culture medium. We also reconstructed extravasation of tumor and inflammatory cells, and circulation inside spheroids including endothelial cells and human lung fibroblasts. In conclusion, this system is a promising tool to elucidate the mechanisms of various biological processes related to vascular flow.

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Tissue culture on a chip: Developmental biology applications of self‐organized capillary networks in microfluidic devices

Cited by 18 publications

References 101 publications

Mathematical modeling for meshwork formation of endothelial cells in fibrin gels

Mathematical modeling for meshwork formation of endothelial cells in fibrin gels

Microphysiological systems in early stage drug development: Perspectives on current applications and future impact

A new perfusion culture method with a self-organized capillary network

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