Microvascularized tumor organoids-on-chips: advancing preclinical drug screening with pathophysiological relevance

Lim, Jae Yol; Ching, Hanna; Yoon, Jeong‐Kee; Jeon, Noo Li; Kim, Yong Tae

doi:10.1186/s40580-021-00261-y

Cited by 52 publications

(38 citation statements)

References 212 publications

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“…Thus, the lack of the biomechanical manipulation has been recognized as a critical limitation to the further development of the matured organoids. To address this problem, a number of studies have recently established the microfluidic culture system that can mimic in vivo-like microenvironments to generate the matured human organoids [ 19 ]. Lee et al has developed a stomach-on-a-chip model using the peristaltic pump that could mimic the luminal flow and rhythmic contraction of the stomach in vivo [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip

et al. 2021

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Kidney organoids derived from the human pluripotent stem cells (hPSCs) recapitulating human kidney are the attractive tool for kidney regeneration, disease modeling, and drug screening. However, the kidney organoids cultured by static conditions have the limited vascular networks and immature nephron-like structures unlike human kidney. Here, we developed a kidney organoid-on-a-chip system providing fluidic flow mimicking shear stress with optimized extracellular matrix (ECM) conditions. We demonstrated that the kidney organoids cultured in our microfluidic system showed more matured podocytes and vascular structures as compared to the static culture condition. Additionally, the kidney organoids cultured in microfluidic systems showed higher sensitivity to nephrotoxic drugs as compared with those cultured in static conditions. We also demonstrated that the physiological flow played an important role in maintaining a number of physiological functions of kidney organoids. Therefore, our kidney organoid-on-a-chip system could provide an organoid culture platform for in vitro vascularization in formation of functional three-dimensional (3D) tissues.

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Section: Introductionmentioning

confidence: 99%

Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip

et al. 2021

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“…Chen et al biofabricated in vitro human 3D vascular cancer model where perfusion and microcirculation of tumor cells are tracked and monitored over time through confocal microscopy [161]. Lim et al have recently reviewed microvascularized aggregates as a various 3D cancer models for drug screening [163].…”

Section: Micro-sized Aggregates and Microspheres/ Microbeadsmentioning

confidence: 99%

Prevascularized Micro-/Nano-Sized Spheroid/Bead Aggregates for Vascular Tissue Engineering

et al. 2021

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Efficient strategies to promote microvascularization in vascular tissue engineering, a central priority in regenerative medicine, are still scarce; nano- and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering. Capillaries are the smallest type and in numerous blood vessels, which are distributed densely in cardiovascular system. To mimic this microvascular network, specific cell components and proangiogenic factors are required. Herein, advanced biofabrication methods in microvascular engineering, including extrusion-based and droplet-based bioprinting, Kenzan, and biogripper approaches, are deliberated with emphasis on the newest works in prevascular nano- and micro-sized aggregates and microspheres/microbeads.

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“…A cutting-edge tool in PDO modeling is the organoid-on-a-chip technology that guarantees high-throughput screening tests with optimized and standardized culture conditions reducing potential differences in organoid size, shape, and geometry. The integration of this organoid-on-a-chip with microfluidic technology using continuously perfused chambers further improved the biomimicry of the model reproducing the microvascular system of large-scale tumors ( 56 ).…”

Section: Pdo Modeling To Study Pancreatic Precursor Lesionsmentioning

confidence: 99%

Pancreatic Cancer Patient-Derived Organoid Platforms: A Clinical Tool to Study Cell- and Non-Cell-Autonomous Mechanisms of Treatment Response

et al. 2021

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For many years, cell lines and animal models have been essential to improve our understanding of the basis of cell metabolism, signaling, and genetics. They also provided an essential boost to cancer drug discovery. Nevertheless, these model systems failed to reproduce the tumor heterogeneity and the complex biological interactions between cancer cells and human hosts, making a high priority search for alternative methods that are able to export results from model systems to humans, which has become a major bottleneck in the drug development. The emergent human in vitro 3D cell culture technologies have attracted widespread attention because they seem to have the potential to overcome these limitations. Organoids are unique 3D culture models with the ability to self-organize in contained structures. Their versatility has offered an exceptional window of opportunity to approach human cancers. Pancreatic cancers (PCs) patient-derived-organoids (PDOs) preserve histological, genomic, and molecular features of neoplasms they originate from and therefore retain their heterogeneity. Patient-derived organoids can be established with a high success rate from minimal tissue core specimens acquired with endoscopic-ultrasound-guided techniques and assembled into platforms, representing tens to hundreds of cancers each conserving specific features, expanding the types of patient samples that can be propagated and analyzed in the laboratory. Because of their nature, PDO platforms are multipurpose systems that can be easily adapted in co-culture settings to perform a wide spectrum of studies, ranging from drug discovery to immune response evaluation to tumor-stroma interaction. This possibility to increase the complexity of organoids creating a hybrid culture with non-epithelial cells increases the interest in organoid-based platforms giving a pragmatic way to deeply study biological interactions in vitro. In this view, implementing organoid models in co-clinical trials to compare drug responses may represent the next step toward even more personalized medicine. In the present review, we discuss how PDO platforms are shaping modern-day oncology aiding to unravel the most complex aspects of PC.

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Microvascularized tumor organoids-on-chips: advancing preclinical drug screening with pathophysiological relevance

Cited by 52 publications

References 212 publications

Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip

Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip

Prevascularized Micro-/Nano-Sized Spheroid/Bead Aggregates for Vascular Tissue Engineering

Pancreatic Cancer Patient-Derived Organoid Platforms: A Clinical Tool to Study Cell- and Non-Cell-Autonomous Mechanisms of Treatment Response

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