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Drug efficacy evaluation on the in vivo CDX model. (A) Tumor growth curves on the in vivo CDX model with or without drug treatment. Pemetrexed, tirapazamine and 5-FU were injected into the HCT15, A375 and SNU-1 xenografted models, respectively. Values are presented as means ± S.D. (B) Images of excised tumor tissues with or without drug treatment after sacrificing the mice at the end of the experiments. (C) The in vivo T/C values from our experiments. The T/C threshold of 40% was labeled in the red dotted line.
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Two-dimensional (2D) tumor model has always poorly predicted drug response of animal model due to the lack of recapitulation of tumor microenvironment. Establishing a biomimetic, controllable, and cost-effective three-dimensional (3D) model and large-scale validation of its in vivo predictivity has shown promise in bridging the gap between the 2D t...
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... performed a live/dead assay on the 3D cultured HCT116 and H460 cells after being treated by the DOX. The live cells were stained in green, and the dead cells were in red (Supplementary Figure S6). The percentage of the dead cells in the drug treatment groups were significantly higher than that in negative control groups. ...
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... regression (T/C) on the pemetrexed-treated HCT15 xenografted model was calculated to be 92%. The higher T/C values were also observed on the tirapazaminetreated A375 model with 88.9%, and the fluorouracil (5-FU)-treated SNU-1 model with 78% (Figures 6A,B). The in vivo T/C values from our study and previous reports were summarized in Table 1. ...
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... in vivo T/C values from our study and previous reports were summarized in Table 1. According to the T/C and TGI thresholds, only 2 out of 40 tests showed effective on the CDX model, which are the pemetrexed-treated MM.1S xenografted model and PRMI-8226 xenografted model ( Figure 6C). The efficacy results from the 2D model, 3D model, and CDX model are also summarized in Table 1. ...
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Ovarian cancer is a devastating disease due to the late diagnosis of advanced stage disease and high recurrence rates. Thus, new long-lasting, efficient drugs are needed. Since chimeric antigen receptor (CAR)-expressing T cell treatments have led to efficient and persisting anti-tumor responses, our study aimed to design and characte...
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... These difficulties have impeded the establishment of an animal orthotopic esophageal tumor model. Therefore, there is increasing interest in the development of a 3D in vitro culture model for bridging the research gap between 2D culture and animal xenogeneic models [13,14]. Presently, there are efforts to develop 3D esophageal cancer models to replicate the tumor-specific cellular and matrix microenvironments based on the tissue engineering to esophagus tissue for 2-4 h with gentle agitation at 4 • C. ...
The lack of physiologically relevant human esophageal cancer models has as a result that many esophageal cancer studies are encountering major bottleneck challenges in achieving breakthrough progress. To address the issue, here we engineered a 3D esophageal tumor tissue model using a biomimetic decellularized esophageal matrix in a customized bioreactor. To obtain a biomimetic esophageal matrix, we developed a detergent-free, rapid decellularization method to decellularize porcine esophagus. We characterized the decellularized esophageal matrix (DEM) and utilized the DEM for the growth of esophageal cancer cell KYSE30 in well plates and the bioreactor. We then analyzed the expression of cancer-related markers of KYSE30 cells and compared them with formalin-fixed, paraffin-embedded (FFPE) esophageal squamous cell carcinoma (ESCC) tissue biospecimens. Our results show that the detergent-free decellularization method preserved the esophageal matrix components and effectively removed cell nucleus. KYSE30 cancer cells proliferated well on and inside the DEM. KYSE30 cells cultured on the DEM in the dynamic bioreactor show different cancer marker expressions than those in the static well plate, and also share some similarities to the FFPE-ESCC biospecimens. These findings built a foundation with potential for further study of esophageal cancer behavior in a biomimetic microenvironment using this new esophageal cancer model.
The safety of nanomaterials, whether they are made of natural or artificial substances, represents a significant challenge because nanotechnology, as a young and up-and-coming field, is developing very quickly, while nanotoxicology and nanoecotoxicology are falling behind. Since the production, use, and consequently, the exposure of people to nanomaterials is increasing significantly, the acquisition of data on potential acute and chronic toxicity plays a crucial role. It is known that nanomaterials due to their high surface-to-volume ratio, high reactivity, and unique physical, chemical, and biological properties exhibit a greater risk of toxicity than the corresponding bulk material and that is why a comprehensive assessment of the toxicity of nanoparticles should always be done prior to their use. We develop 3D cell models as a new in vitro methodological approach for nanoparticle (geno)toxicity assessment to better understand the impact nanomaterials have on environmental and human health. Currently, as a part of our ongoing study, core-shell iron nanoparticles are being examined, where the core consists of FeO, and the shell is made of Fe3O4. So far, in vitro cyto- and genotoxicity were assessed in the human hepatocellular carcinoma cell line HepG2, using the ATP assay and the comet assay, respectively, but due to ongoing genotoxicity testing and reservations about data publishing, the results will not be presented in this scientific contribution. Keywords: 3D cell models; 2D cell models; Cytotoxicity; DNA damage; Genotoxicity; Iron-based nanoparticles
Microvasculature plays a crucial role in human physiology and is closely related to various human diseases. Building in vitro vascular networks is essential for studying vascular tissue behavior with repeatable morphology and signaling conditions. Engineered 3D microvascular network models, developed through advanced microfluidic-based techniques, provide accurate and reproducible platforms for studying the microvasculature in vitro, an essential component for designing organ-on-chips to achieve greater biological relevance. By optimizing the microstructure of microfluidic devices to closely mimic the in vivo microenvironment, organ-specific models with healthy and pathological microvascular tissues can be created. This review summarizes recent advancements in in vitro strategies for constructing microvascular tissue and microfluidic devices. It discusses the static vascularization chips’ classification, structural characteristics, and the various techniques used to build them: growing blood vessels on chips can be either static or dynamic, and in vitro blood vessels can be grown in microchannels, elastic membranes, and hydrogels. Finally, the paper discusses the application scenarios and key technical issues of existing vascularization chips. It also explores the potential for a novel organoid chip vascularization approach that combines organoids and organ chips to generate better vascularization chips.
Multicellular spheroids, which mimic the natural organ counterparts, allow the prospect of drug screening and regenerative medicine. However, their application is hampered by low processing efficiency or limited scale. This study introduces an efficient method to drive rapid multicellular spheroid formation by a cellulose nanofibril matrix. This matrix enables the facilitated growth of spheroids (within 48 h) through multiple cell assembly into size-controllable aggregates with well-organized physiological microstructure. The efficiency, dimension, and conformation of the as-formed spheroids depend on the concentration of extracellular nanofibrils, the number of assembled cells, and the heterogeneity of cell types. The above strategy allows the robust formation mechanism of compacted tumoroids and hepatocyte spheroids.
Scientific knowledge in the field of cell biology and mechanobiology heavily leans on cell-based in vitro experiments and models that favor the examination and comprehension of certain biological processes and occurrences across a variety of environments. Cell culture assays are an invaluable instrument for a vast spectrum of biomedical and biophysical investigations. The quality of experimental models in terms of simplicity, reproducibility, and combinability with other methods, and in particular the scale at which they depict cell fate in native tissues, is critical to advancing the knowledge of the comprehension of cell-cell and cell-matrix interactions in tissues and organs. Typically, in vitro models are centered on the experimental tinkering of mammalian cells, most often cultured as monolayers on planar, two-dimensional (2D) materials. Notwithstanding the significant advances and numerous findings that have been accomplished with flat biology models, their usefulness for generating further new biological understanding is constrained because the simple 2D setting does not reproduce the physiological response of cells in natural living tissues. In addition, the co-culture systems in a 2D stetting weakly mirror their natural environment of tissues and organs. Significant advances in 3D cell biology and matrix engineering have resulted in the creation and establishment of a new type of cell culture shapes that more accurately represents the in vivo microenvironment and allows cells and their interactions to be analyzed in a biomimetic approach. Contemporary biomedical and biophysical science has novel advances in technology that permit the design of more challenging and resilient in vitro models for tissue engineering, with a particular focus on scaffold- or hydrogel-based formats, organotypic cultures, and organs-on-chips, which cover the purposes of co-cultures. Even these complex systems must be kept as simplified as possible in order to grasp a particular section of physiology too very precisely. In particular, it is highly appreciated that they bridge the space between conventional animal research and human (patho)physiology. In this review, the recent progress in 3D biomimetic culturation is presented with a special focus on co-cultures, with an emphasis on the technological building blocks and endothelium-based co-culture models in cancer research that are available for the development of more physiologically relevant in vitro models of human tissues under normal and diseased conditions. Through applications and samples of various physiological and disease models, it is possible to identify the frontiers and future engagement issues that will have to be tackled to integrate synthetic biomimetic culture systems far more successfully into biomedical and biophysical investigations.
