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Engineering The Tumor Microenvironment Using Microfluidics
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Book Synopsis Engineering the Tumor Microenvironment Using Microfluidics by : loannis K. Zervantonakis
Download or read book Engineering the Tumor Microenvironment Using Microfluidics written by loannis K. Zervantonakis and published by . This book was released on 2013 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: 90% of cancer related deaths are due to metastatic disease and there is a need for a better understanding of cell-microenvironment interactions to identify new therapeutic targets. A key step during cancer metastasis is cancer cell intravasation (entry of cancer cells into the blood vessels) that results in tumor cell dissemination into distant organs. During this process, tumor cells navigate a complex microenvironment and interact with multiple cell types. This thesis is aimed to develop a microfluidic-based intravasation assay that allows for direct observation of tumor cell motility combined with quantitation of the endothelial barrier function. Compared with traditional in vitro assays, microfluidic assays enable "user-defined" design of the cellular and acellular microenvironment with spatio-temporal control and live high-resolution imaging. Formation of confluent endothelial layers in the device was confirmed with immunofluorescence staining for endothelial cell-cell junctions and we compared our diffusive permeability values with published in vivo and in vitro data. We employ this microfluidic assay to investigate the role of endothelial barrier function during tumor cell intravasation to address a critical question in cancer research: does tumor cell intravasation require a leaky endothelium? To induce vessel leakiness we perturb the barrier using biochemical factors, endothelial cells with low expression of basement membrane proteins and signaling with macrophages. Under all these conditions, tumor cell intravasation rates increased and we confirmed these results for multiple tumor cell types. Characterization of macrophage secreted factors and M1/M2 polarization status, identified that blocking macrophage-secreted TNF-a restored endothelial permeability and reduced tumor cell intravasation. In agreement with these results, we also found that the number and dynamics of tumor-endothelial interactions were dependent on endothelial barrier function. A novel feature of the developed assay is the ability to image in real-time the process of tumor cell intravasation, while also enabling accurate control and quantitation of the functional characteristics of the endothelial barrier. Our results not only demonstrate the important role of cell-cell paracrine signaling and biochemical factors in regulating tumor cell intravasation, but also have important implications for strategies aimed to disrupt or normalize vasculature in vivo. Keywords: 3D Microfluidics, Endothelial permeability, Cancer cell Intravasation, Macrophages.
Book Synopsis Microfluidics and Biosensors in Cancer Research by : David Caballero
Download or read book Microfluidics and Biosensors in Cancer Research written by David Caballero and published by Springer Nature. This book was released on 2022-06-27 with total page 599 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a comprehensive overview of the development and application of microfluidics and biosensors in cancer research, in particular, their applications in cancer modeling and theranostics. Over the last decades, considerable effort has been made to develop new technologies to improve the diagnosis and treatment of cancer. Microfluidics has proven to be a powerful tool for manipulating biological fluids with high precision and efficiency and has already been adopted by the pharmaceutical and biotechnology industries. With recent technological advances, particularly biosensors, microfluidic devices have increased their usefulness and importance in oncology and cancer research. The aim of this book is to bring together in a single volume all the knowledge and expertise required for the development and application of microfluidic systems and biosensors in cancer modeling and theranostics. It begins with a detailed introduction to the fundamental aspects of tumor biology, cancer biomarkers, biosensors and microfluidics. With this knowledge in mind, the following sections highlight important advances in developing and applying biosensors and microfluidic devices in cancer research at universities and in the industry. Strategies for identifying and evaluating potent disease biomarkers and developing biosensors and microfluidic devices for their detection are discussed in detail. Finally, the transfer of these technologies into the clinical environment for the diagnosis and treatment of cancer patients will be highlighted. By combining the recent advances made in the development and application of microfluidics and biosensors in cancer research in academia and clinics, this book will be useful literature for readers from a variety of backgrounds. It offers new visions of how this technology can influence daily life in hospitals and companies, improving research methodologies and the prognosis of cancer patients.
Book Synopsis Ex Vivo Engineering of the Tumor Microenvironment by : Amir R. Aref
Download or read book Ex Vivo Engineering of the Tumor Microenvironment written by Amir R. Aref and published by Springer. This book was released on 2016-12-09 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume will outline how to recreate the tumor microenvironment, to culture primary tumors without the need for developmental priming factors, and to deliver targeted therapeutics in a manner that recapitulates pharmacokinetics in vivo. Much of what may be learned from this volume will aid in understanding many aspects of the enhanced study of tumor cell biology in a physiologic context, open new avenues for drug screening and biomarker development, and accelerate the preclinical evaluation of novel personalized medicine strategies for patients in real time.
Book Synopsis Microfluidic Tools to Recapitulate the Tumor Microenvironment by : Luis Fernando Alonzo
Download or read book Microfluidic Tools to Recapitulate the Tumor Microenvironment written by Luis Fernando Alonzo and published by . This book was released on 2014 with total page 76 pages. Available in PDF, EPUB and Kindle. Book excerpt: Treatments for cancer remain elusive due, in large part, to the dynamic and unstable genome of most cancer cells. More recently it has become evident that tumor growth and progression to metastasis depends on the ability to recruit normal cells, such as endothelial cells, fibroblasts, as key accomplices. These observations suggest that selective targeting of normal cells, which have a stable genome, could be an effective alternative or complimentary approach in the overall management of the disease. Understanding of such relationship is key for the design of anti-metastatic therapeutics. However, much of the data reported in this field has been performed in xenograft models and/or 2D cultures; which are limited by the number of controllable variables, extrapolation to human tumor physiology, and not amenable for a high-throughput design. This work aims to address the role of the tumor microenvironment using a novel in vitro platform that combines microfluidic and tissue engineering technology to create a 3D tumor microarray in which the tumors receive their nutrients through perfused human microcirculation. This model is capable of replicating the physiology of the in vivo tumor microenvironment; thus providing relevant physiological results. Most importantly, the impact of creating an in vitro 3D metastasis model with perfused human capillary bed could significantly enhance high-throughput anti-metastatic drug screening.
Book Synopsis Fabrication of Collagen-based Microfluidic Devices for in Vitro Study of Tumor Microenvironment by : Rhys James Michna
Download or read book Fabrication of Collagen-based Microfluidic Devices for in Vitro Study of Tumor Microenvironment written by Rhys James Michna and published by . This book was released on 2016 with total page 82 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microfluidic technology has led to the development of advanced in vitro tumor platforms that overcome the challenges of in vivo animal and in vitro two dimensional models. This paper presents platform designs and methods used to develop in vitro models that replicate the tumor microenvironment. Features of these platforms include a continuous endothelium that allows for cell-cell interactions between vasculature and tumor cells. Additionally, we can recreate the abnormal shear stresses and the tortuous vasculature seen in patient tumors. Various methods such as subtractive, additive, and soft lithography techniques have been used by groups to manufacture complex microfluidic tumor models. A novel platform for fabrication of a single endothelialized microchannel encased within a collagen hydrogel hosting breast cancer cells was developed and utilized to study the influence of cellular interaction on transport phenomenon through vasculature in a hyperpermeable tumor microenvironment. We have confirmed the platforms ability to recapitulate physiological features of the tumor microenvironment and demonstrated the influence of tumor endothelial interactions on transport. Additionally, a second platform capable of combining lithographic techniques with additive tissue engineering methods was used to create endothelialized microfluidic networks that capture the more complex geometries of tumor microvasculature. By modeling microvascular networks after in vivo tumors we are able to create patient specific in vitro platforms that can be used to develop personalized patient treatments.
Book Synopsis Micro and Nanoengineering of the Cell Microenvironment by : Ali Khademhosseini
Download or read book Micro and Nanoengineering of the Cell Microenvironment written by Ali Khademhosseini and published by Artech House. This book was released on 2008 with total page 647 pages. Available in PDF, EPUB and Kindle. Book excerpt: Supported with 140 illustrations, the volume exhaustively covers the micro- and nano-system technologies involved in developing cell-based bioengineering applications. You get full details on efforts to engineer the soluble and insoluble cell microenvironments, including the latest advances in microfluidic devices, surface patterning, 3D scaffolds, and techniques for engineering cellular mechanical properties and topography.
Book Synopsis Biomaterial Based Approaches to Study the Tumour Microenvironment by : Jessica O Winter
Download or read book Biomaterial Based Approaches to Study the Tumour Microenvironment written by Jessica O Winter and published by Royal Society of Chemistry. This book was released on 2022-12-07 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: The tumour microenvironment is increasingly recognized as an important contributor to cancer progression and treatment. However, most cancer studies continue to be performed in 2D tissue culture dishes that do not capture the characteristics of the tumour niche. This book provides an introduction to the rich chemical, topographical, and mechanical cues in the tumour microenvironment and then introduces readers to bioengineering strategies, including scaffold design and synthesis, chemical signalling and delivery, and co-culture, microfluidics, and organ-on-a-chip tools that can be used to mimic tumour microenvironment features. This book also includes discussion of emerging imaging methods compatible with tumour microenvironment mimicking biomaterials and discusses applications of such models in immuno-oncology, metastasis, and drug screening. Edited by two leaders in the field, this book will appeal to graduate students and researchers working in biomaterials science, chemical and biomedical engineering departments.
Book Synopsis Nanotechnology for Microfluidics by : Xingyu Jiang
Download or read book Nanotechnology for Microfluidics written by Xingyu Jiang and published by John Wiley & Sons. This book was released on 2020-09-08 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on microfluidics with applications in nanotechnology. The first part summarizes the recent advances and achievements in the field of microfluidic technology, with emphasize on the the influence of nanotechnology. The second part introduces various applications of microfluidics in nanotechnology, such as drug delivery, tissue engineering and biomedical diagnosis.
Book Synopsis Biomaterials- and Microfluidics-Based Tissue Engineered 3D Models by : J. Miguel Oliveira
Download or read book Biomaterials- and Microfluidics-Based Tissue Engineered 3D Models written by J. Miguel Oliveira and published by Springer Nature. This book was released on 2020-04-13 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contributed volume reviews the latest advances on relevant 3D tissue engineered in vitro models of disease making use of biomaterials and microfluidics. The main focus of this book is on advanced biomaterials and microfluidics technologies that have been used in in vitro mimetic 3D models of human diseases and show great promise in revolutionizing personalized medicine. Readers will discover important topics involving biomaterials and microfluidics design, advanced processing techniques, and development and validation of organ- and body-on-a-chip models for bone, liver, and cancer research. An in depth discussion of microfabrication methods for microfluidics development is also provided. This work is edited by two truly multidisciplinary scientists and includes important contributions from well-known experts in their fields. The work is written for both early stage and experienced researchers, and well-established scientists enrolled in the fields of biomaterials, microfluidics, and tissue engineering, and is especially suited to those who wish to become acquainted with the principles and latest developments of in vitro models of diseases, such as professionals working in pharma, medicine, and engineering.
Download or read book Tumor Organoids written by Shay Soker and published by Humana Press. This book was released on 2017-10-20 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
Book Synopsis The Microfluidic Intravital Window by : Logan Butt
Download or read book The Microfluidic Intravital Window written by Logan Butt and published by . This book was released on 2018 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis In Vitro Study of Cancer Cell Extravasation in Microfluidic Platform by : Jessie Sungyun Jeon
Download or read book In Vitro Study of Cancer Cell Extravasation in Microfluidic Platform written by Jessie Sungyun Jeon and published by . This book was released on 2014 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer metastases arise from the cancer cells that disseminate from the primary tumor, intravasate into the vascular system and eventually transmigrate across the endothelium into to a secondary site through a process of extravasation. Microfluidic systems have a major advantage in studying cancer extravasation since they can mimic aspects of the 3D in vivo situation in a controlled environment while simultaneously providing in situ imaging capabilities for visualization, thereby enabling quantification of cell-cell and cell-matrix interactions. Moreover, microfluidics enable parametric study of multiple factors in controlled and repeatable conditions. This thesis describes novel 3D microfluidic models to mimic the tumor microenvironment and vasculature during cancer cell extravasation in order to investigate the critical steps of extravasation. First, a general non-organ-specific cancer cell extravasation model is developed in which the endothelial cells that cover the walls of the microfluidic channel represent the vessel endothelium, and the entire extravasation process including tumor cell adhesion to the endothelium and subsequent transmigration can be observed. A second model is then introduced to mimic organ-specific extravasation and investigate the preference of certain types of cancer to target specific organs for metastass. The improved model was used to study the specificity of human breast cancer metastases to bone, by recreating a vascularized bone-mimicking microenvironment. The tri-culture system allowed us to study the transendothelial migration of highly metastatic breast cancer cells and to monitor their behavior within the bone-like matrix. Next, functional microvascular networks were generated in the microfluidic system through vasculogenesis with addition of mural cells and pro-angiogenic factors to better replicate the normal physiological vasculature of the remote site for metastasis. Lastly, the vasculogenesis approach was combined with the bone-mimicking model to develop a functional osteo-cell conditioned vasculature model to study physiologically relevant extravasation in a bone-like microenvironment. In addition to the quantification of extravasation rates and subsequent tumor cell migration into the model tissue, the vascular networks were characterized by measuring permeability, and immunostaining of proteins secreted by osteo-cell and mural cell markers confirmed the creation of microenvironments and the presence of multiple cell types within the matrix. This study provides novel 3D in vitro quantitative data on cancer cell extravasation and micrometastasis of breast cancer cells within a bone-mimicking microenvironment. The developed microfluidic system represents an advanced in vitro model to study complex biological phenomena such as extravasation involving functional microvascular networks under organ-specific conditions and demonstrates the potential value of microfluidic technologies to better understand cancer biology and screen for new therapeutics.
Book Synopsis Engineering the Tumor Microenvironment by : Marcel Alexander Heinrich
Download or read book Engineering the Tumor Microenvironment written by Marcel Alexander Heinrich and published by . This book was released on 2022 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Microfluidic Systems for Cancer Diagnosis by : Jose L. Garcia-Cordero
Download or read book Microfluidic Systems for Cancer Diagnosis written by Jose L. Garcia-Cordero and published by Springer Nature. This book was released on 2023-06-10 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed volume explores recent developments in microfluidics technologies for cancer diagnosis and monitoring. The book is divided into two sections that delve into techniques for liquid biopsy for cancer diagnosis and platforms for precision oncology or personalized medicine in order to create effective patient avatars for testing anti-cancer drugs. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Microfluidic Systems for Cancer Diagnosis serves as an ideal guide that will be helpful to either replicate the construction of microfluidic devices specifically developed for cancer diagnosis or to catalyze development of new and better cancer diagnostic devices.
Book Synopsis Modularized Microfluidics to Study Biological Interactions with Spatial-temporal Specificity by : Jiaquan Yu
Download or read book Modularized Microfluidics to Study Biological Interactions with Spatial-temporal Specificity written by Jiaquan Yu and published by . This book was released on 2019 with total page 126 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer prognosis is a challenging yet inevitable task. The challenge of providing an accurate prediction of cancer resides, at least partially, on not being able to represent the complex interactions between cancer and its host immune system. While the immune system is normally able to detect and eliminate cancerous cells, some cancer cells are able to initiate tumorigenesis by evading immune surveillance. In many cases, immune cells and the tumor microenvironment are conditioned by the tumor to play an active, protective role in supporting its progression. Yet our knowledge of the various immune components (e.g. neutrophils, macrophages, NK cells, T-cells) and the specific roles they play in immunoselection is still an area of active debate and inquiry. Currently, there are not adequate tools to answer important questions. How does the conditioning of immune cells happen and how does it support tumor progression? What is the role of a dynamic microenvironment (e.g. tissue-resident macrophages) in tumor adaptation? What factors and cells determine whether a tumor will survive, or even take advantage of, an immune response toward it? The process of immunoselection and the dynamic interaction between cells and their microenvironment can only be assessed through a trans-scale, multi-cellular model. In this work, we bring together expertise across the physical sciences-cancer biology-oncology continuum to improve our understanding of the role of the immune system in cancer - specifically the process of immune- cell conditioning and its associated tissue remodeling. This work not only provides insight into the concurrent processes of immune cell conditioning and tumor progression but also establishes various engineering systems to enable further investigation of cancer-immune interaction and the first step toward the ultimate goal of patient-specific cancer prognosis.
Book Synopsis Microfluidics for Cellular Applications by : Gerardo Perozziello
Download or read book Microfluidics for Cellular Applications written by Gerardo Perozziello and published by Elsevier. This book was released on 2023-04-13 with total page 433 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microfluidics for Cellular Applications describes microfluidic devices for cell screening from a physical, technological and applications point-of-view, presenting a comparison with the cell microenvironment and conventional instruments used in medicine. Microfluidic technologies, protocols, devices for cell screening and treatment have reached an advanced state but are mainly used in research. Sections break them down into practical applications and conventional medical procedures and offers insights and analysis on how higher resolutions and fast operations can be reached. This is an important resource for those from an engineering and technology background who want to understand more and gain additional insights on cell screening processes. Outlines the major applications of microfluidic devices in medicine and biotechnology Assesses the major challenges of using microfluidic devices in terms of complexity of the control set-up, ease of use, integration capability, automation level, analysis throughput, content and costs Describes the major fabrication techniques for assembling effective microfluidic devices for bioapplications
Book Synopsis Engineering the Vascular Tumor Microenvironment by : Seema Mai Ehsan
Download or read book Engineering the Vascular Tumor Microenvironment written by Seema Mai Ehsan and published by . This book was released on 2014 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer drug development remains a costly and inefficient endeavor that often translates to limited clinical success. While most therapies focus on stalling the growth of or eradicating tumor cells directly, the microenvironment in which these cells inhabit plays a hugely influential role in defining drug efficacy and disease progression. The supporting vasculature system as well as the interstitial extracellular matrix are particularly consequential to the transport, distribution, and uptake of therapeutics. While it is known that the host microenvironment may enable the advancement of malignancy and even the development of resistance, much of the mechanistic understanding by which this regulation occurs remains unclear. This is due in part to a lack of physiologically relevant models, though advancements in the emerging field of "tumor engineering" are beginning to challenge this. The transition away from incompatible animal models and simplified two-dimensional cultures has brought about the creation of advanced three-dimensional models in order to better simulate and test the microenvironmental characteristics that define human cancers. Nonetheless, few systems are able to capture the full range of authentic, complex in vivo events such as neovascularization, intravasation, and variable oxygen distribution. This work will explore the details of developing biologically-inspired, highly controlled in vitro tumor microenvironments to replicate and investigate these events. Such systems have the potential to mediate successful translation of preclinical research to clinical significance, while also providing mechanistic insight into the early stages of tumor progression and metastasis.
