Three Dimensional Human Organotypic Models for Biomedical Research


Book Description

This edited volume discusses the application of very diverse human organotypic models in major areas of biomedical research. The authors lay a main focus on infectious diseases, cancer, allergies, as well as drug/vaccine discovery and toxicology studies. Representing a valid alternative to laboratory animals, these models are relevant for most areas of translational research. As the contemporary research shows, many human tissues can today be cultivated in vitro and used for several research objectives. This book provides an unprecedented overview of recent developments in an exciting field of research methodology. It is a reference guide for scientists in both academia and industry. Readers can update their knowledge and get hands-on recommendations on how to set up an organotypic model in their lab. Chapters 'Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers' and 'Human Organotypic Models for Anti-infective Research' of this book are available open access under a CC BY 4.0 license at link.springer.com.




Organotypic Models in Drug Development


Book Description

This book provides latest findings in organotypic models in drug development and provides the scientific resonance needed in an emerging field of research in disciplines, such as molecular medicine, physiology, and pathophysiology. Today the research on human-based test systems has gained major interest and funding in the EU and the US has increased over the last years. Moreover, so-called 3R (reduce, replace, refine animal experiments) centres have been established worldwide.




Tumor Organoids


Book Description

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.




Concepts and Models for Drug Permeability Studies


Book Description

This book intends to be an updated compilation of the most important buccal, gastric, intestinal, pulmonary, nasal, vaginal, ocular, skin and blood-brain barrier in vitro models for predicting the permeability of drugs. Concepts and Models for Drug Permeability Studies focuses on different approaches and comprises of various models. Each model describes the protocol of seeding and conservation, the application for specific drugs, and takes into account the maintenance of physiologic characteristics and functionality of epithelium, from the simplest immortalized cell-based monoculture to the most complex engineered-tissue models. Chapters also discuss the equivalence between in vitro cell and tissue models and in vivo conditions, highlighting how each model may provisionally resemble a different drug absorption route. - Updated information regarding the most recent in vitro models to study the permeability of drugs - Short and concise chapters covering all the biological barriers with interest in drug permeability - A combination of bibliographic information related with individual models and footnote instructions of technical procedures for construction of cell and tissue-based models - Simple and clear scientific content, adaptable for young scientists and experimented researchers




The Impact of Food Bioactives on Health


Book Description

“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.




Use of 3D Models in Drug Development and Precision Medicine: Advances and Outlook


Book Description

Dr. Davide Staedler is CEO of TIBIO Sagl, a consulting company, and chief scientific officer of Scitec Research S.A., a private analytical laboratory. All other Topic Editors declare no competing interests with regards to the Research Topic subject.




Blood-Brain Barrier in Drug Discovery


Book Description

Focused on central nervous system (CNS) drug discovery efforts, this book educates drug researchers about the blood-brain barrier (BBB) so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery. • Written by world experts to provide practical solutions to increase brain penetration or minimize CNS side-effects • Reviews state-of-the-art in silico, in vitro, and in vivo tools to assess brain penetration and advanced CNS drug delivery strategies • Covers BBB physiology, medicinal chemistry design principles, free drug hypothesis for the BBB, and transport mechanisms including passive diffusion, uptake/efflux transporters, and receptor-mediated processes • Highlights the advances in modelling BBB pharmacokinetics and dynamics relationships (PK/PD) and physiologically-based pharmacokinetics (PBPK) • Discusses case studies of successful CNS and non-CNS drugs, lessons learned and paths to the market




Review of the Fialuridine (FIAU) Clinical Trials


Book Description

In June 1993 a clinical trial of fialuridine (FIAU), a promising new medication for hepatitis B, was abruptly terminated when one of the 15 out-patients participating in the National Institutes of Health (NIH) study was suddenly hospitalized with liver failure. Although all the remaining patients were contacted and told to stop taking their medication, six more subsequently developed severe toxicity. Five patients died, and two others were probably saved from death only by having liver transplants. In response to a request from the Secretary of the Department of Health and Human Services, the IOM committee has analyzed the FIAU clinical trials, making recommendations for additional safeguards for the conduct of future clinical trials. This evaluation included the review of documents pertaining to investigational new drug submissions, protocols and consent forms from other clinical trials, as well as information available from other clinical and preclinical experience with compounds related to FIAU and its parent drug, fiacitibine (FIAC), which is metabolized to FIAU. The committee does not seek to affix responsibility for the adverse outcome of this NIH trial, but instead focuses on whether any rules or procedures governing the clinical trials process itself need to be changed, and if so, what burdens or costs such changes might place on future clinical trials.




Microfluidic Cell Culture Systems


Book Description

The fields of microfluidics and BioMEMS are significantly impacting cell biology research and applications through the application of engineering solutions to human disease and health problems. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. This new professional reference applies the techniques of microsystems to cell culture applications. The authors provide a thoroughly practical guide to the principles of microfluidic device design and operation and their application to cell culture techniques. The resulting book is crammed with strategies and techniques that can be immediately deployed in the lab. Equally, the insights into cell culture applications will provide those involved in traditional microfluidics and BioMEMS with an understanding of the specific demands and opportunities presented by biological applications. The goal is to guide new and interested researchers and technology developers to the important areas and state-of-the-practice strategies that will enhance the efficiency and value of their technologies, devices and biomedical products.




Drug Absorption Studies


Book Description

This is a well thought-out, highly practical text covering contemporary ‘in vitro’ techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.