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SELECTBIO Conferences 3D-Culture, Organoids and Organs-on-Chips 2021

3D-Culture, Organoids and Organs-on-Chips 2021 Agenda

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Monday, 22 March 2021


Conference Registration, Materials Pick-Up, Morning Coffee and Pastries

Session Title: Conference Opening Session


Roger KammKeynote Presentation

Strategies For in vitro Perfusion of iPSC-derived Organoids: A Tough Nut to Crack
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Now that organoids can be generated for a variety of organs and tissues from induced pluripotent stem cells, there is tremendous interest in developing methods to connect an external perfusion system to an internal vasculature.  Success in this quest would help facilitate continuous perfusion, leading to improved viability and functionality of the developing organ, and supporting the introduction of therapeutics for drug screening and development.  For more than 5 years, we have had the capability to grow self-assembled microvascular beds, or pattern small vessels within various hydrogels.  Methods are also increasingly available to induce the growth vascular networks inside of the organoid. To date, however, it has proved challenging to induce anastomosis between these two networks and enable continuous perfusion. In this presentation, different methods will be discussed that hold promise to address this critical problem.


Josué  SznitmanKeynote Presentation

Advanced In vitro Inhalation Lung-on-Chip Platforms For Preclinical Research
Josué Sznitman, Associate Professor, Technion – Israel Institute of Technology, Israel

With rapid advances, the development of lung-on-chip platforms is offering novel avenues for more realistic inhalation assays in pharmaceutical research, and an opportunity to depart from traditional in vitro lung assays. As advanced models capturing the cellular pulmonary make-up at an air-liquid interface (ALI), lung-on-chips emulate both morphological features and biological functionality of the airway barrier with the ability to integrate respiratory breathing motions and ensuing tissue strains. Such in vitro systems allow importantly to mimic more realistic physiological respiratory flow conditions, with the opportunity to integrate physically-relevant transport determinants of aerosol inhalation therapy, i.e. recapitulating the pathway from airborne flight to deposition on the airway lumen. In this presentation, we discuss recent developments in our group on devising such advanced human-relevant lung-on-chip models that mimic in situ-like inhalation assays with endpoints geared at cytotoxicity, respiratory diseases and therapies.


Morning Break


Michael ShulerKeynote Presentation

Body on a Chip: A Transformative Approach to Improve Drug Development
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University, President & CEO, Hesperos, Inc., United States of America

A physiologically representative, multi-organ microphysiological systems (MPS) based on human tissues (also known as “human-on-a-chip” TM) may be a transformative technology to improve the selection of drug candidates most likely to earn regulatory approval from clinical trials. Such microscale systems combine organized human tissues with the techniques of microfabrication based on PBPK (Physiologically Based Pharmacokinetic) models.

I will describe such systems being constructed at Hesperos and at Cornell. They are “self-contained” in that they can operate independently and do not require external pumps as is the case with many other microphysiological systems. They are “low cost”, in part, because of the simplicity and reliability of operation. They maintain a ratio of fluid (blood surrogate) to cells that is more physiologic than in many other in vitro systems allowing the observation of the effects of not only drugs but their metabolites. While systems can be sampled to measure the concentrations of drugs, metabolites, or biomarkers, they also can be interrogated in situ for functional responses such as electrical activity, force generation, or integrity of barrier function. Operation up to 28 days has been achieved allowing observation of both acute and chronic responses with serum free media.


Nancy AllbrittonKeynote Presentation

Intestine on Chip for Normal Physiology and Disease Models
Nancy Allbritton, Frank and Julie Jungers Dean of the College of Engineering and Professor of Bioengineering, University of Washington in Seattle, United States of America

Organ-on-chips are miniaturized devices that arrange living cells to simulate functional subunits of tissues and organs. These microdevices provide exquisite control of tissue microenvironment for the investigation of organ-level physiology and disease. A 3D polarized epithelium using primary human or mouse gastrointestinal stem cells was developed to fully recapitulate gastrointestinal epithelial architecture and physiology. A planar monolayer comprised of stem/proliferative and differentiated primary cells is cultured on a shaped hydrogel scaffold with an array of crypt-like structures replicating the intestinal architecture. Imposition of chemical gradients across the crypt long axis yields a polarized epithelium with a stem-cell niche and differentiated cell zone. The stem cells proliferate, migrate and differentiate along the crypt axis as they do in vivo. A dense mucus layer is formed on the luminal epithelial surface that is impermeable to bacteria and acts a barrier to toxins. An oxygen gradient across the tissue mimic permits luminal culture of anaerobic bacteria while maintaining an oxygenated stem cell niche. This in vitro human colon crypt array replicates the architecture, luminal accessibility, tissue polarity, cell migration, and cellular responses of in vivo intestinal crypts. A thick impenetrable layer of mucus with biophysical parameters similar to that of a living human can be formed for epithelial cell-microbe studies. Intestinal biopsy samples can be used to populate these constructs to produce patient-specific tissues for personalized medicine and disease modeling. This bioanalytical platform is envisioned as a next-generation system for assay of microbiome-behavior, drug-delivery and toxin-interactions with the intestinal epithelia.


Protein FluidicsAutomated 3D Cell-Based Assays Using a Novel Flowchip System
Evan Cromwell, President & CEO, Protein Fluidics

There is an increasing interest in using three-dimensional (3D) cell structures for modeling tumors, organs, and tissue to accelerate translation research. Significant progress has been made in formation of such structures to recapitulate the in vivo environment but performing complex assays with them can be challenging.  Organoids can be subject to loss or damage from pipettes during common steps such as media exchange, supernatant sampling, or immunofluorescence staining.  We present here results from automated organoid assays using a Pu·MA System for research in oncology therapeutics, single organoid secretion, and metabolite sampling.  The system uses a novel flowchip that contains organoid samples connected to multiple reservoirs via microfluidic channels.  Assay reagents are transferred in and out of the sample well without loss of or damage to the organoids.  The bottom of the sample chamber is thin optically clear plastic compatible with high resolution fluorescence imaging.  The whole system can be kept in an incubator allowing long term cellular assays to be performed.  In a first example, effects of anti-cancer drugs on cancer spheroids were assayed using high content imaging.  Confocal imaging allowed 3D resolution of spheroid structures and complex analysis of cytotoxic effects.  In addition, conditioned media was removed and analyzed for VEGF.  In a second example, triple negative breast cancer (TNBC) patient-derived organoids were used for disease modeling.  This novel assay system using microfluidics enables automation of 3D cell-based cultures that mimic in vivo conditions, performs multi-dosing protocols and multiple media exchanges, provides gentle and convenient handling of spheroids and organoids, and allows a wide range of assay detection modalities.


Lunch Break

Session Title: Trends in Organoids and Organs-on-Chip, circa 2021


Tumor-on-a-Chip Platforms for Analyzing Intact Tumor Biopsies
Albert Folch, Professor of Bioengineering, University of Washington, United States of America

Cancer remains a major healthcare challenge worldwide. It is now well established that cancer cells constantly interact with fibroblast cells, endothelial cells, immune cells, signaling molecules, and the extracellular matrix in the tumor microenvironment (TME). Present tools to study drug responses and the TME have not kept up with drug testing needs. Oncology drugs typically take 10 years and cost an average of 1 billion dollars to develop. The number of clinical trials of combination therapies has been climbing at an unsustainable rate, with 3,362 trials launched since 2006 to test PD-1/PD-L1-targeted monoclonal antibodies alone or in combination with other agents. We have developed a microfluidic platform (called Oncoslice) for the delivery of multiple drugs with spatiotemporal control to live tumor biopsies, which retain the TME. We have developed the use of Oncoslice for the delivery of small-molecule cancer drug panels to glioblastoma (GBM) xenograft slices as well as to slices from patient tumors (GBM and colorectal liver metastasis). In addition, we have developed a precision slicing methodology that allows for producing large numbers of cuboidal micro-tissues (“cuboids”) from a single tumor biopsy. We have been able to trap cuboids in arrays of microfluidic traps in a multi-well platform. This work will potentially allow for the high-throughput application of drugs to intact human tumor tissues.


Molecular DevicesOrganoids For Disease Modeling and In Vitro Assessment of Drug Effects by High-Content Imaging and 3D Analysis
Oksana Sirenko, Sr. Imaging Applications Scientist, Molecular Devices

3D cell models representing different tissues were successfully used for studying complex biological effects, tissue architecture, and functionality. While complexity of 3D models remains a hurdle for the wider adoption in research and drug screening, significant progress has been made in developing tools to automate the culture, monitoring, and analysis of these structures. This enabled an increase in quality of information, throughput, and precision of complex biological assays. We describe automated cell culture and high-content imaging methods that allow monitoring and characterization of growth and differentiation of lung organoids, as well as toxicity and drug effects. Increase in size and complexity of developing organoids was monitored during eight weeks of development. We demonstrated concentration-dependent toxicity effects of several drugs that have been known to cause lung damage. In addition, responses to several anti-cancer drugs were monitored in 3D tumoroids derived from primary tumor tissues.  Advanced image analysis allowed 3D reconstitution and complex analysis of organoid structures, characterization of cell morphology and viability, as well as determining expression level of differentiation markers. Image analysis included traditional and Machine Learning-based tools to increase the ability to discern important biological information from the complex multi-dimensional datasets. These quantitative characterization of organoids morphology can be used for studying disease phenotypes and compound effects in complex assay models.


Mid-Afternoon Break


Kevin HealyKeynote Presentation

Microphysiological Systems as Testbeds Spanning Drug Discovery to Organ Preservation
Kevin Healy, Jan Fandrianto and Selfia Halim Distinguished Professorship in Engineering, University of California, Berkeley, United States of America

Our work has emphasized creating both healthy and diseased model organ systems, called microphysiological systems, to address the costly and inefficient drug discovery process. While organ chips are poised to disrupt the drug development process and significantly reduce the cost of bringing a new drug candidate to market, organ chip technology is much more robust and creates a whole new paradigm in how to study biology, and advances medicine in revolutionary ways. Emerging use of microphysiological systems span organ preservation, biomaterials development, gene editing, and environmental toxicology. This presentation will discuss examples of exploiting microphysiological systems as unique testbeds for these cutting edge areas.


Linda GriffithKeynote Presentation

Humanizing Models of Liver Diseases
Linda Griffith, Professor, Massachusetts Institute of Technology (MIT), United States of America

The growing commercial availability of high quality cryopreserved human hepatocytes, expansion of hepatocytes via organoid technology, and advances in derivation of hepatic organoids from iPSC, along with advances in mesofluidic platforms that provide gut-liver interactions, open opportunities for building accessible human disease models.   This talk will describe conceptual and technical considerations in building models of liver metabolic and inflammatory diseases, including cell sourcing, culture media design, microphysiological system platform design, incorporation of immune cells, and cross talk with the gut with examples illustrating how to integrate multi-omic data.


John WikswoKeynote Presentation

What Do We Need to Make Microphysiological Systems Drug Assays Massively Parallel?
John Wikswo, Gordon A. Cain University Professor, A.B. Learned Professor of Living State Physics; Founding Director, Vanderbilt Institute for Integrative Biosystems, Vanderbilt University, United States of America

Organs-on-chips, organoids and coupled microphysiological systems (MPS) will never reach the level of automation possible with single-pass, high throughput screening of million-compound drug libraries using robots for acoustic seeding, feeding, and dosing-of cells or spheroids in 1536 well plates, followed by either end-point imaging or acoustic delivery of media to a mass spectrometer. Nor should they. But one can wonder exactly how many MPS devices could be created, maintained, and analyzed by an appropriate robotic perfusion system. We will describe a convergence of microfluidic, robotic, and analytic technologies that could easily service a thousand organ-chips or 10,000 separate organoids in a 42U telecom rack/incubator, each undergoing different pharmacokinetic exposures and dynamic metabolomic readouts.


Close of Day 1 of the Conference

Tuesday, 23 March 2021


Morning Coffee, Pastries and Networking


Terry RissConference Chair

Live-Cell Kinetic Assays of 3D Cultures to Monitor Cell Health and Metabolite Levels Used to Select Samples For Further Analysis
Terry Riss, Senior Product Manager, Cell Health, Promega Corporation, United States of America

With the increased use of physiologically relevant models comes the need for sensitive assay methods to monitor health of cells cultured in a 3D environment. Live-cell kinetic assays are available to interrogate 3D culture models and report the number of live cells, dead cells, apoptotic cells, or key metabolite levels remaining in the medium. Because the live-cell kinetic assays do not kill the cells, data from real-time monitoring of changes in viability or metabolite utilization can be set as a threshold to cherry pick a subset of individual samples for more time consuming image recording and computational analysis using high content screening. We will describe how we use the power of luminescence detection to overcome the limitations in sensitivity and create live-cell kinetic assays to monitor 3D culture models.


Bioprinting of 3D Extracellular Matrix Models For Cancer Research
MoonSun Jung, Senior Research Officer, Children’s Cancer Institute Australia, Australia

Cancer is a leading cause of mortality and morbidity worldwide. However, the exact molecular mechanisms underlying the tumorigenesis and metastasis are still poorly understood. Conventional 2-dimentional (2D) in vitro models are widely used for cancer research. These monolayer models however cannot accurately recapitulate the characteristics of native tumor microenvironment, including the cell-cell and cell-matrix interactions that cancer cells experience in vivo. 3D bioprinting provides an exciting opportunity to create in vitro tumor microenvironment with living cells using extracellular matrix (ECM) materials. However, it is still rare that 3D bioprinted models use biomaterials with high biocompatibility and tunability of the ECM-like properties. In collaboration with Inventia Life Science, we have developed 3D matrix models by printing small droplets of cells and matrix components using their drop-on-demand 3D bioprinter. With this technology, we are currently investigating the diverse aspects of cancer behaviours in response to environmental changes such as stiffness and biological molecules and identifying optimal biomimic ECM conditions for different cancer types.


Morning Break


Multi-Organ Interconnected Human-on-a-Chip Systems to Develop Phenotypic Disease Models For In Vivo Predictions
James Hickman, Professor, Nanoscience Technology, Chemistry, Biomolecular Science and Electrical Engineering, University of Central Florida; Chief Scientist, Hesperos, United States of America

I will describe such systems being constructed that are guided in their design by PBPK models. They are “self-contained” in that they can operate independently and do not require external pumps as is the case with other microphysiological systems. They are “low cost”, in part, because of the simplicity and reliability of operation allowing the observation of the effects of not only drugs but their metabolites. While systems can be sampled to measure the concentrations of drugs, metabolites, or biomarkers, they also can be interrogated in situ for functional responses such as electrical activity, force generation, or integrity of barrier function. Operation up to 28 days has been achieved allowing observation of both acute and chronic responses with serum free media. We have worked with various combinations of internal organ modules (liver, fat, neuromuscular junction, skeletal muscle, cardiac, bone marrow, blood vessels and brain) and barrier tissues (e.g. skin, GI tract, blood brain barrier, lung and kidney) and immune components. The use of microelectrode arrays to monitor electrically active tissues (cardiac and neuronal) and micro cantilevers (muscle) have been demonstrated. Most importantly, these technical advances allow prediction of both a drug’s potential efficacy and toxicity (side-effects) in pre-clinical studies.


Formation of Uniform, Size-Controllable Multicellular Tumor Spheroids in Polydimethylsiloxane-Coated Well Plates
Jirina Kroupová, Researcher, University of Chemistry and Technology, Prague, Czech Republic


Lunch Break


Lung and Mammary Microphysiological Systems
Shuichi Takayama, Professor, Georgia Research Alliance Eminent Scholar, and Price Gilbert, Jr. Chair in Regenerative Engineering and Medicine, Georgia Institute of Technology & Emory University School of Medicine, United States of America

This presentation will describe efforts to develop higher throughput physiologically relevant cellular systems using devices, materials, and organoid engineering.

Session Title: Interactive Poster Session

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