Key to the development of the HUB Organoid Technology was the discovery of adult stem cells by Hans Clevers. Provided with the appropriate growth factors, the adult stem cells form a polarized epithelium in which stem cells and their differentiated offspring maintain their natural hierarchy and function. In addition, the organoids are genetically stable during prolonged culture. Subsequently, we developed Organoid technology for most other epithelia. High-establishment efficiency means that we can use the Organoid Technology to generate disease models from virtually all patients.

Primary organotypic cultures need to be robust and reproducible with limited donor-to-donor variability to advance discovery research toward complex functional tissue biology, yet donor-to-donor variability has not been characterized systematically for many human organoid systems. We established intestinal organoid cultures from adult stem cells of healthy donors and characterized inter- and intra-culture variability. We found that differentiation patterns were consistent among cultures and passages, producing all expected intestinal cell types.

Electrical activity of brain, retina or muscle organoids can now be easily characterized, label free, at single-cell resolution by using MaxWell Biosystems’ high-density microelectrode array (HD-MEA) technology. We will present HD-MEA results from human iPSC-derived organoids modeling different brain compartments and demonstrate the potential of the technology for drug testing.

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) is a technically-focused organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader R&D community.

Alzheimer’s disease leads to amyloid deposits along cerebral vasculature which impair the function of the blood-brain barrier (BBB) and accelerate cognitive degeneration. APOE4 is the strongest risk factor for cerebrovascular amyloid pathology (CAA) and Alzheimer’s disease (AD); however, the underlying pathogenic mechanisms are unknown. We developed an in vitro model of the human BBB that revealed the mechanisms through which APOE4 predisposes amyloid deposition, and uncovered new therapeutic opportunities for CAA and AD.

Our goal is to develop and validate a precision medicine therapeutic profiling technology by implementing rapid, cost-effective, physiologically relevant, functional 3D models of brain cancer for phenotypic evaluation of anti-cancer drugs. This combined with molecular pathology has been implemented into clinically pertinent information, which will improve the quality and speed of a physician’s decision-making for drug selection in treating cancer in a patient-specific manner.

NeuCyte develops hiPSC-based in vitro systems for modeling of neurological diseases. The platform allows for efficient testing of drugs in a scalable environment of human neurophysiology early in the drug development process. We will share how NeuCyte applies it for modeling disorders such as epilepsy, Fragile X syndrome and more.

We have developed a gut-in-a-dish model from 3D organoids isolated from the intestinal specimens of healthy and diseased patients. This model consisting of epithelial cells, immune cells, and microbes could be utilized to investigate mechanisms for gastrointestinal inflammatory diseases, both oncogenic and non-oncogenic. A semi-HTP format of the model can be useful for the identification of new diagnostic and therapeutic targets, personalization of therapies through Phase “0” human trials, and much more.

The NCATS 3D Tissue Bioprinting Laboratory is using biofabrication techniques together with quantitative assay technologies to produce architecturally and physiologically validated normal and diseased 3D tissue models in multi-well plate format to create an in-tissue assay platform for drug discovery and development that will be more clinically predicative than current in vitro cellular models. The presentation will describe the approach used at NCATS to create a portfolio of biofabricated 3D tissue models of the retina, skin, ometum and brain, as in tissue assay platforms for disease modeling, including age-related macular degeneration, atopic dermatitis and several cancers, and for pharmacological testing of toxicity and efficacy effects.

Organoid cultures have redefined the limits of biological data that can be obtained in vitro. Learn about how IntestiCult™ Organoid Differentiation Medium drives the differentiation of organoids and organoid-derived monolayer cultures into a more functional, differentiated epithelium that better recapitulates the cellular composition and function of the human intestinal epithelium.

Microphysiological systems are bioengineered in vitro tools that mimic the 3D structure and function of human organ systems and have been developed to improve the predictive assessment of the safety and efficacy of promising therapeutics. The use of human-derived cells and tissues have increased the utility of tissue chips towards modeling diseases and for clinical trials on chips to inform human trial design. This presentation will focus on the latest advances in this promising technology.

There is a great need to understand the synergy between the areas of translational and regulatory science research as they pertain to microphysiological systems and their application in evaluating safety and efficacy for therapeutic indications for different disease areas. My presentation will focus on identifying these areas of synergy and focus on the development of microphysiological systems that are a best fit for different applications.

iPSC-CM model systems have relatively immature phenotypes, critically limiting their ability to model human function. Here, we will present novel, high-throughput bioengineering methods to improve the maturity and predictivity of 2D and 3D iPSC-CM model systems that can be implemented in a cell-, instrument-, and assay-agnostic manner.