Intestinal Organoids: New Tools to Comprehend the Virulence of Bacterial Foodborne Pathogens

Foodborne diseases cause high morbidity and mortality worldwide. Understanding the relationships between bacteria and epithelial cells throughout the infection process is essential to setting up preventive and therapeutic solutions. The extensive study of their pathophysiology has mostly been performed on transformed cell cultures that do not fully mirror the complex cell populations, the in vivo architectures, and the genetic profiles of native tissues. Following advances in primary cell culture techniques, organoids have been developed. Such technological breakthroughs have opened a new path in the study of microbial infectious diseases, and thus opened onto new strategies to control foodborne hazards. This review sheds new light on cellular messages from the host–foodborne pathogen crosstalk during in vitro organoid infection by the foodborne pathogenic bacteria with the highest health burden. Finally, future perspectives and current challenges are discussed to provide a better understanding of the potential applications of organoids in the investigation of foodborne infectious diseases.

Gradient biomimetic platforms for neurogenesis studies

There is a need for the development of new cellular therapies for the treatment of many diseases, with the central nervous system (CNS) currently an area of specific focus. Due to the complexity and delicacy of its biology, there is currently a limited understanding of neurogenesis and consequently a lack of reliable test platforms, resulting in several CNS based diseases having no cure. The ability to differentiate pluripotent stem cells into specific neuronal sub-types may enable scalable manufacture for clinical therapies, with a focus also on the purity and quality of the cell population. This focus is targeted towards an urgent need for the diseases that currently have no cure, e.g. Parkinson’s disease. Differentiation studies carried out using traditional 2D cell culture techniques are designed using biological signals and morphogens known to be important for neurogenesis in vivo. However, such studies are limited by their simplistic nature, including a general poor efficiency and reproducibility, high reagent costs and an inability to scale-up the process to a manufacture-wide design for clinical use. Biomimetic approaches to recapitulate a more in vivo-like environment are progressing rapidly within this field, with application of bio(chemical) gradients presented both as 2D surfaces and within a 3D volume. This review focusses on the development and application of these advanced extracellular environments particularly for the neural niche. We emphasise the progress that has been made specifically in the area of stem cell derived neuronal differentiation. Increasing developments in biomaterial approaches to manufacture stem cells will enable the improvement of differentiation protocols, enhancing the efficiency and repeatability of the process with a move towards up-scaling. Progress in this area brings these techniques closer to enabling the development of therapies for the clinic.

Design and Fabrication of Organ-on-Chips: Promises and Challenges

The advent of the miniaturization approach has influenced the research trends in almost all disciplines. Bioengineering is one of the fields benefiting from the new possibilities of microfabrication techniques, especially in cell and tissue culture, disease modeling, and drug discovery. The limitations of existing 2D cell culture techniques, the high time and cost requirements, and the considerable failure rates have led to the idea of 3D cell culture environments capable of providing physiologically relevant tissue functions in vitro. Organ-on-chips are microfluidic devices used in this context as a potential alternative to in vivo animal testing to reduce the cost and time required for drug evaluation. This emerging technology contributes significantly to the development of various research areas, including, but not limited to, tissue engineering and drug discovery. However, it also brings many challenges. Further development of the technology requires interdisciplinary studies as some problems are associated with the materials and their manufacturing techniques. Therefore, in this paper, organ-on-chip technologies are presented, focusing on the design and fabrication requirements. Then, state-of-the-art materials and microfabrication techniques are described in detail to show their advantages and also their limitations. A comparison and identification of gaps for current use and further studies are therefore the subject of the final discussion.

Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells

The brain is our most complex and least understood organ. Animal models have long been the most versatile tools available to dissect brain form and function; however, the human brain is highly distinct from that of standard model organisms. In addition to existing models, access to human brain cells and tissues is essential to reach new frontiers in our understanding of the human brain and how to intervene therapeutically in the face of disease or injury. In this review, we discuss current and developing culture models of human neural tissue, outlining advantages over animal models and key challenges that remain to be overcome. Our principal focus is on advances in engineering neural cells and tissue constructs from human pluripotent stem cells (PSCs), though primary human cell and slice culture are also discussed. By highlighting studies that combine animal models and human neural cell culture techniques, we endeavor to demonstrate that clever use of these orthogonal model systems produces more reproducible, physiological, and clinically relevant data than either approach alone. We provide examples across a range of topics in neuroscience research including brain development, injury, and cancer, neurodegenerative diseases, and psychiatric conditions. Finally, as testing of PSC-derived neurons for cell replacement therapy progresses, we touch on the advancements that are needed to make this a clinical mainstay.

Emerging liver organoid platforms and technologies

Building human organs in a dish has been a long term goal of researchers in pursue of physiologically relevant models of human disease and for replacement of worn out and diseased organs. The liver has been an organ of interest for its central role in regulating body homeostasis as well as drug metabolism. An accurate liver replica should contain the multiple cell types found in the organ and these cells should be spatially organized to resemble tissue structures. More importantly, the in vitro model should recapitulate cellular and tissue level functions. Progress in cell culture techniques and bioengineering approaches have greatly accelerated the development of advance 3-dimensional (3D) cellular models commonly referred to as liver organoids. These 3D models described range from single to multiple cell type containing cultures with diverse applications from establishing patient-specific liver cells to modeling of chronic liver diseases and regenerative therapy. Each organoid platform is advantageous for specific applications and presents its own limitations. This review aims to provide a comprehensive summary of major liver organoid platforms and technologies developed for diverse applications.

Internet of Things Architecture for High Throughput Biology

New cell culture techniques have led to complex tissue models in biological experiments. For example, 3-D cerebral organoids provide a more realistic model of the human cortical tissue. However, these cell culture experiments are restricted by high costs and limited labor. A massively scalable and cost efficient platform for tissue experiments would benefit genomics, neuroscience, and translational medicine by enabling advanced high throughput tissue screens. Cloud computing and the Internet of Things (IoT) provide new tools for managing multiple experiments in parallel that are remotely controlled through automation. We introduce a cloud-based IoT architecture that takes advantage of these tools to offer an environment where researchers can run thousands of cell culture experiments at once. This technology allows studies with cell cultures to be performed at scales far beyond a single lab setting, democratizing access to advanced tissue models and enabling new avenues of research.

Imitating Hypoxia and Tumor Microenvironment with Immune Evasion by Employing Three Dimensional in vitro Cellular Models: Impressive Tool in Drug Discovery

: The heterogeneous tumor microenvironment is exceptionally perplexing and not wholly comprehended. Different multifaceted alignments lead to the generation of oxygen destitute situations within the tumor niche that modulate numerous intrinsic tumor microenvironments. Disentangling these communications is vital for scheming practical therapeutic approaches that can successfully decrease tumor allied chemotherapy resistance by utilizing the innate capability of the immune system. Several research groups have concerned with a protruding role for oxygen metabolism along with hypoxia in the immunity of healthy tissue. Hypoxia in addition to hypoxia-inducible factors (HIFs) in the tumor microenvironment plays an important part in tumor progression and endurance. Although numerous hypoxia-focused therapies have shown promising outcomes both in vitro and in vivo these outcomes have not effectively translated into clinical preliminaries. Distinctive cell culture techniques have utilized as an in vitro model for tumor niche along with tumor microenvironment and proficient in more precisely recreating tumor genomic profiles as well as envisaging therapeutic response. To study the dynamics of tumor immune evasion, three-dimensional (3D) cell cultures are more physiologically important to the hypoxic tumor microenvironment. Recent research has revealed new information and insights into our fundamental understanding of immune systems, as well as novel results that have been established as potential therapeutic targets. There are a lot of patented 3D cell culture techniques which will be highlighted in this review. At present notable 3D cell culture procedures in the hypoxic tumor microenvironment, discourse open doors to accommodate both drug repurposing, advancement, and divulgence of new medications and will deliberate the 3D cell culture methods into standard prescription disclosure especially in the field of cancer biology which will be discussing here.

Advances in Adoptive Cellular Therapy (ACT)

Adoptive T cell therapy (ACT) is getting acknowledged as the Advanced Therapy Medicinal Products (ATMPs) in many countries and it has evolved as one of the newest regimens to treat cancer. Developed gradually by the basic understanding of cells, involved in innate and adaptive immunity, ACT has emerged as one of the successful immunotherapies in recent times. It broadly includes various cell types such as stem cells, T cells, dendritic cells and Natural Killer cells. By the applications of genetic engineering and advanced cell culture techniques, these cells from patients’ blood, can be manipulated to train them for better efficacy against specific tumor cells. However, only some cells’ subsets have shown promising regression for certain cancer cells types. To understand the reason behind this, technical knowledge about the tumor antigens presentation, tumor microenvironment (TME), hosts’ immune responses and possible issues in the manufacturing of adoptive cellular material for infusion in patients are being explored further. This chapter brings together development of immune cells from basic research to clinical use, newer approaches which have been taken to address the resistance of ACT and future promises of this therapy.