Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network

Sano, Emi; Mori, Chihiro; Nashimoto, Yuji; Yokokawa, Ryuji; Kotera, Hidetoshi; Torisawa, Yu-suke

doi:10.1063/1.5027183

Cited by 47 publications

(37 citation statements)

References 37 publications

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“…Functional hydrogels can mimic native ECM with tunable chemical compositions and mechanical properties, which are conductive to replicate the complex microenvironment of human organs. Hydrogels acted as 3D matrices or scaffolds have been incorporated into OOC to engineer human tissues with multicellular architecture and organ‐specific functions by spatial control of microenvironment cues . A variety of 3D parenchymal tissues in hydrogel‐based organs‐on‐chips have been reported, such as liver, heart, skeletal muscle, intestine, and nasal mucosa …”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…84 Osteo-differentiated mesenchymal stem cells, mineralized hydroxyapatite-incorporated ECM, and ex vivo bone scaffolds have all been shown to elicit relevant cell behavior in in vitro bone tissue models. [85][86][87][88] Incorporation of perfusable vascular networks in these models allows for cancer cells to be flowed though, recapitulating extravasation events at the metastatic site. Bioreactors can be used to create complex, mature tissue constructs for seeding as well as to expose seeded scaffolds to tunable, physiological compressive forces to observe colonization behavior.…”

Section: Step 4 and 5: Extravasation And Colonizationmentioning

confidence: 99%

Endothelial PAI-1 (Plasminogen Activator Inhibitor-1) Blocks the Intrinsic Pathway of Coagulation, Inducing the Clearance and Degradation of FXIa (Activated Factor XI)

Puy

Ngo

Pang

et al. 2019

ATVB

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While considerable progress has been made in studying genetic and cellular aspects of metastasis with in vitro cell culture and in vivo animal models, the driving mechanisms of each step of metastasis are still relatively unclear due to their complexity. Moreover, little progress has been made in understanding how cellular fitness in one step of the metastatic cascade correlates with ability to survive other subsequent steps. Engineered models incorporate tools such as tailored biomaterials and microfabrication to mimic human disease progression, which when coupled with advanced quantification methods permit comparisons to human patient samples and in vivo studies. Here, we review novel tools and techniques that have been recently developed to dissect key features of the metastatic cascade using primary patient samples and highly representative microenvironments for the purposes of advancing personalized medicine and precision oncology. Although improvements are needed to increase tractability and accessibility while faithfully simulating the in vivo microenvironment, these models are powerful experimental platforms for understanding cancer biology, furthering drug screening, and facilitating development of therapeutics.

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“…A similar chip design was used for investigating the effects of physical cues on sprouting; in this case, interstitial flow was generated that promoted sprouting against the direction of the flow [21]. These type of systems have also been used in the research on tumour vasculature and the effect of different drugs on the vasculature and tumour progression [75][76][77][78][79].…”

Section: Angiogenesis-based Platformsmentioning

confidence: 99%

Recapitulating the Vasculature Using Organ-On-Chip Technology

Pollet

Toonder

2020

Bioengineering

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The development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.

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Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network

Cited by 47 publications

References 37 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Endothelial PAI-1 (Plasminogen Activator Inhibitor-1) Blocks the Intrinsic Pathway of Coagulation, Inducing the Clearance and Degradation of FXIa (Activated Factor XI)

Recapitulating the Vasculature Using Organ-On-Chip Technology

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