Blood Flow Characterization in a Perfused Collagen Vessel Bioreactor Using X-Ray Micro-PIV

Author(s):  
Elizabeth Voigt ◽  
Cara F. Buchanan ◽  
M. Nichole Rylander ◽  
Pavlos Vlachos

Newly developed cancer therapies must pass through a series of increasingly complex testing regimens before obtaining FDA approval as valid treatments. The costs of these tests increase rapidly as the physiological accuracy of the platform increases, from initial proof-of-concept in static tissue cultures, to treatment of animal models, and ultimately to human clinical trials. Three-dimensional engineered blood-perfused tumor models are becoming increasingly important as intermediate platforms for the study and treatment of cancer, as they are superior to static two-dimensional cultures in their reproduction of relevant physiological conditions and are inexpensive in comparison to animal models. Because of this, the design of well-characterized adaptable in vitro vascular tumor models has become a central objective of the emerging field of tumor engineering. Characterization of the flow within three-dimensional tumor models is critical for quantifying fluid shear stress and determining its role in pivotal tumor development processes such as tumor cell angiogenesis and metastasis. Ultimately, this knowledge will provide new avenues for therapeutic modulation of the tumor microenvironment.

Proceedings ◽  
2020 ◽  
Vol 40 (1) ◽  
pp. 44
Author(s):  
Demirtaş

The engineering of convenient three-dimensional (3D) in vitro tumor models presents many challenges, but they are increasingly identifying as one of the best preclinical drug-screening platforms and a developed method to research cancer in controlled conditions in the lab. Recently advanced 3D bioprinting techniques can be enhanced to produce biomimetic and complex tumor structures. The native tumors have complex structures originating from different extracellular matrix materials, cell types, and biomolecules. To obtain this, multifactorial bio-inks to consist of multiple hydrogel biomaterials (alginate, collagen, fibrin, gelatin, and chitosan as natural bio-inks), patient-derived different types of cancer cells, and soluble factors have been advanced. 3D bioprinting of live human cells has shown that effective in vitro replication of tumor biology is achievable. Several last research outline current improvements in the use of bio-printed tumor models used in cancer research, enhancing a new boundary for the understanding of tumor biology and the progress of cancer therapies.


Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].


2018 ◽  
Author(s):  
Lawrance Chandra ◽  
Dana C Borcherding ◽  
Dawn Kingsbury ◽  
Todd Atherly ◽  
Yoko M Ambrosini ◽  
...  

AbstractBackgroundLarge animal models, such as the dog, are increasingly being used over rodent models for studying naturally occurring diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between currently used animal models (e.g. mouse) and humans, and expand the translational potential of the dog model, we developed a three dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.ResultsOrganoids were propagated from isolation of adult intestinal stem cells (ISC) from whole jejunal tissue as well as endoscopically obtained duodenal, ileal and colonic biopsy samples of healthy dogs and GI cases, including inflammatory bowel disease (IBD) and intestinal carcinomas. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization and transmission electron microscopy, and organoids mimicked the in vivo tissue environment. Physiological relevance of the enteroid system was defined using functional assays such as Optical Metabolic Imaging (OMI), the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research.ConclusionsIn summary, our findings establish the canine GI organoid systems as a novel model to study naturally occurring intestinal diseases in dogs and humans. Furthermore, canine organoid systems will help to elucidate host-pathogen interactions contributing to GI disease pathogenesis.


Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 481
Author(s):  
Tarek Saydé ◽  
Omar El Hamoui ◽  
Bruno Alies ◽  
Karen Gaudin ◽  
Gaëtane Lespes ◽  
...  

Three-dimensional cell culture has revolutionized cellular biology research and opened the door to novel discoveries in terms of cellular behavior and response to microenvironment stimuli. Different types of 3D culture exist today, including hydrogel scaffold-based models, which possess a complex structure mimicking the extracellular matrix. These hydrogels can be made of polymers (natural or synthetic) or low-molecular weight gelators that, via the supramolecular assembly of molecules, allow the production of a reproducible hydrogel with tunable mechanical properties. When cancer cells are grown in this type of hydrogel, they develop into multicellular tumor spheroids (MCTS). Three-dimensional (3D) cancer culture combined with a complex microenvironment that consists of a platform to study tumor development and also to assess the toxicity of physico-chemical entities such as ions, molecules or particles. With the emergence of nanoparticles of different origins and natures, implementing a reproducible in vitro model that consists of a bio-indicator for nano-toxicity assays is inevitable. However, the maneuver process of such a bio-indicator requires the implementation of a repeatable system that undergoes an exhaustive follow-up. Hence, the biggest challenge in this matter is the reproducibility of the MCTS and the associated full-scale characterization of this system’s components.


Micromachines ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 35 ◽  
Author(s):  
Meng-Tsan Tsai ◽  
Bo-Huei Huang ◽  
Chun-Chih Yeh ◽  
Kin Fong Lei ◽  
Ngan-Ming Tsang

Investigation of tumor development is essential in cancer research. In the laboratory, living cell culture is a standard bio-technology for studying cellular response under tested conditions to predict in vivo cellular response. In particular, the colony formation assay has become a standard experiment for characterizing the tumor development in vitro. However, quantification of the growth of cell colonies under a microscope is difficult because they are suspended in a three-dimensional environment. Thus, optical coherence tomography (OCT) imaging was develop in this study to monitor the growth of cell colonies. Cancer cell line of Huh 7 was used and the cells were applied on a layer of agarose hydrogel, i.e., a non-adherent surface. Then, cell colonies were gradually formed on the surface. The OCT technique was used to scan the cell colonies every day to obtain quantitative data for describing their growth. The results revealed the average volume increased with time due to the formation of cell colonies day-by-day. Additionally, the distribution of cell colony volume was analyzed to show the detailed information of the growth of the cell colonies. In summary, the OCT provides a non-invasive quantification technique for monitoring the growth of the cell colonies. From the OCT images, objective and precise information is obtained for higher prediction of the in vivo tumor development.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Caroline Rivera ◽  
Sofia Rivera ◽  
Yohann Loriot ◽  
Marie-Catherine Vozenin ◽  
Eric Deutsch

Lung cancer remains the leading cause of cancer death. Understanding lung tumors physiopathology should provide opportunity to prevent tumor development or/and improve their therapeutic management. Cancer stem cell (CSC) theory refers to a subpopulation of cancer cells, also named tumor-initiating cells, that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signaling pathways specific to lung CSCs may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developingin vitroandin vivomodels may yield reliable tools to better understand CSC abilities and to test new therapeutic targets. Preclinical data on putative CSC targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies.


Sign in / Sign up

Export Citation Format

Share Document