Vascularized Tumor Spheroid-on-a-Chip Model Verifies Synergistic Vasoprotective and Chemotherapeutic Effects

Hu, Zhiwei; Cao, Yuanxiong; Galan, Edgar A.; Hao, Liang; Zhao, Haoran; Tang, Jiayu; Sang, Gan; Wang, Hanqi; Xu, Bing; Ma, Shaohua

doi:10.1021/acsbiomaterials.1c01099

Cited by 33 publications

(28 citation statements)

References 66 publications

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“…The different relative sizes between tumor and vascular tissue in these three models mimic the interaction between tumor and blood vessels at different stages of cancer. A vascularized tumor spheroid-on-a-chip model was developed by Ma’s group to verify synergistic vasoprotective and chemotherapeutic effects ( Figure 4 (Ab)) [ 129 ]. They constructed a perfusion–perfused vascularized tumor spheroid-on-a-chip model.…”

Section: Ooc For Tumor Modelingmentioning

confidence: 99%

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Liu

Zhang

et al. 2022

Biosensors

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Although many studies have focused on oncology and therapeutics in cancer, cancer remains one of the leading causes of death worldwide. Due to the unclear molecular mechanism and complex in vivo microenvironment of tumors, it is challenging to reveal the nature of cancer and develop effective therapeutics. Therefore, the development of new methods to explore the role of heterogeneous TME in individual patients’ cancer drug response is urgently needed and critical for the effective therapeutic management of cancer. The organ-on-chip (OoC) platform, which integrates the technology of 3D cell culture, tissue engineering, and microfluidics, is emerging as a new method to simulate the critical structures of the in vivo tumor microenvironment and functional characteristics. It overcomes the failure of traditional 2D/3D cell culture models and preclinical animal models to completely replicate the complex TME of human tumors. As a brand-new technology, OoC is of great significance for the realization of personalized treatment and the development of new drugs. This review discusses the recent advances of OoC in cancer biology studies. It focuses on the design principles of OoC devices and associated applications in cancer modeling. The challenges for the future development of this field are also summarized in this review. This review displays the broad applications of OoC technique and has reference value for oncology development.

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Section: Ooc For Tumor Modelingmentioning

confidence: 99%

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Liu

Zhang

et al. 2022

Biosensors

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“…To construct vessels with a diameter smaller than 100 μm, the second method, based on endothelial cell self-assembly in hydrogels, has been reported. − After being seeded into hydrogels at appropriate concentrations, endothelial cells can deform and self-assemble into interconnected and perfusable capillary networks. ,,, This approach has been broadly used to build vascularized tissue models on-chip in the last decades. , For example, Offeddu et al reported their work on building a breast cancer metastasis model with this approach and evaluated the role of endothelial cell glycocalyx in tumor cell metastatic extravasation . Furthermore, by providing mechanical and biochemical cues in the hydrogels on such platforms, endothelial cells can migrate and sprout in the hydrogel to form new vessels. ,,, Kim et al demonstrated that the endothelial cells could sense both interstitial flow and growth factor gradient, thus sprout to form new vessels against the flow direction and the growth factor gradient in hydrogel. , Nashimoto et al show that the vascularized tumor model can be constructed by inducing angiogenesis with the spheroids consisting of fibroblasts and tumor cells in hydrogel …”

Section: Introductionmentioning

confidence: 99%

Hierarchical Vessel Network-Supported Tumor Model-on-a-Chip Constructed by Induced Spontaneous Anastomosis

Zhou

Paul

et al. 2023

ACS Appl. Mater. Interfaces

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The vascular system in living tissues is a highly organized system that consists of vessels with various diameters for nutrient delivery and waste transport. In recent years, many vessel construction methods have been developed for building vascularized on-chip tissue models. These methods usually focused on constructing vessels at a single scale. In this work, a method that can build a hierarchical and perfusable vessel networks was developed. By providing flow stimuli and proper HUVEC concentration, spontaneous anastomosis between endothelialized lumens and the self-assembled capillary network was induced; thus, a perfusable network containing vessels at different scales was achieved. With this simple method, an in vivolike hierarchical vessel-supported tumor model was prepared and its application in anticancer drug testing was demonstrated. The tumor growth rate was predicted by combining computational fluid dynamics simulation and a tumor growth mathematical model to understand the vessel perfusability effect on tumor growth rate in the hierarchical vessel network. Compared to the tumor model without capillary vessels, the hierarchical vessel-supported tumor shows a significantly higher growth rate and drug delivery efficiency.

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“…Nashimoto et al combined spheroid culture (formed of lung fibroblasts and HUVECs) with angiogenesis strategies by culturing the spheroid together with endothelial cells in a microfluidic device [13]. Hu et al also produced a perfusable vascularised tumor spheroid by adding it to a microvascularised microfluidic chamber and showing integration between the two structures [14]. Although the number of studies reporting integrated microvascularised tissue models is rapidly increasing, there is a need to increase the range of tissues that can be integrated with microvascularised networks, without impacting their structural and functional performance.…”

Section: Introductionmentioning

confidence: 99%

Vascularised Cardiac Spheroids-on-a-Chip for Testing the Toxicity of Therapeutics

Ciò

Haddrick²,

Gautrot

2023

Preprint

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Microfabricated organ-on-a-chip tissue models are rapidly becoming the gold standard for the testing of safety and efficacy of therapeutics. A broad range of designs has emerged, but recreating microvascularised tissue models remains difficult in many cases. This is particularly relevant to mimic the systemic delivery of therapeutics, to capture the complex multi-step processes associated with trans-endothelial migration, uptake by targeted tissues and associated metabolic response. In this report, we describe the formation of microvascularised cardiac tissue spheroids embedded in microfluidic chips. The embedding of spheroids within vascularised multi-compartment microfluidic chips was investigated to identify the importance of the spheroid processing, and co-culture with pericytes on the integration of the spheroid within the microvascular networks formed. The architecture of the resulting models, the expression of cardiac and endothelial markers and the perfusion of the system was then investigated. The ability to retain beating over prolonged periods of time was quantified, over a period of 25 days, demonstrating not only perfusability but also functional performance of the tissue model. Finally, as a proof-of-concept of therapeutic testing, the toxicity of one therapeutic associated with cardiac disfunction was evaluated, identifying differences between direct in vitro testing on suspended spheroids and vascularised models.

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Vascularized Tumor Spheroid-on-a-Chip Model Verifies Synergistic Vasoprotective and Chemotherapeutic Effects

Cited by 33 publications

References 66 publications

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Recent Advances of Organ-on-a-Chip in Cancer Modeling Research

Hierarchical Vessel Network-Supported Tumor Model-on-a-Chip Constructed by Induced Spontaneous Anastomosis

Vascularised Cardiac Spheroids-on-a-Chip for Testing the Toxicity of Therapeutics

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