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SELECTBIO Conferences Multi-Cellular Engineered Living Systems Summit

Multi-Cellular Engineered Living Systems Summit Agenda



Co-Located Conference Agendas

2D-to-3D Culture and Organoids 2020 | Multi-Cellular Engineered Living Systems Summit | 

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Wednesday, 25 March 2020

08:00

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


Session Title: Multi-Cellular Engineered Living Systems Summit

08:30

Roger KammTerry RissConference Chair

Conference Chairpersons Welcome, Introduction and Topics Addressed
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT)
Terry Riss, Global Strategic Marketing Manager Cell Health, Promega Corporation, United States of America

08:45

Linda GriffithKeynote Presentation

Engineering Mucosal Barriers: From Organoids to Organs–on–Chips
Linda Griffith, Professor, Massachusetts Institute of Technology (MIT), United States of America

Mucosal barriers are the gateways to all internal organs, serving to transport oxygen, nutrients, and waste and at the same time performing enormous feats of protection against infection and other hazardous insults.  The explosion of interest in the human microbiome – especially but not only that in the gut – has driven new interest in building human mucosal barrier models. This talk will highlight three related themes: (i) engineering synthetic microenvironments to expand primary adult epithelial organoids and induce morphogenesis into mucosal barriers (ii) engineering microfluidic devices to create microbial-mucosal interfaces that enable chronic co-culture of the most super strict anaerobes such as Faecalibacterium prausnitzii with a colon mucosal barrier and (iii) interconnection of mucosal barriers with other tissues in systemic circuits to illuminate the role of gut-derived bacterial metabolites on function of other organ systems.  Examples will emphasize how these approaches can be used to model chronic inflammatory diseases.

09:30

Donna MendrickKeynote Presentation

Alternative Models Use: Regulatory Context
Donna Mendrick, Associate Director of Regulatory Activities, US Food and Drug Administration (FDA), United States of America

In 2017 FDA published the Predictive Toxicology Roadmap (https://www.fda.gov/science-research/about-science-research-fda/fdas-predictive-toxicology-roadmap)-a framework for integrating predictive toxicology methods into safety and risk assessments.  FDA welcomes data from alternative methods and is working internally and externally to learn more about technologies such as MPS.  This presentation will provide an overview of MPS work being done within FDA and the actions being taken to help move alternative assays into a regulatory context.

10:15

Morning Coffee Break and Networking

11:00

Peter ErtlKeynote Presentation

Parkinson’s-On-a-Chip: Unravelling the Complexity of Neurodegenerative Diseases Using a Chip-based Midbrain Organoid Model
Peter Ertl, Professor of Lab-on-a-Chip Systems, Vienna University of Technology, Austria

One of the main limitations in neuroscience and in the modeling and understanding of neurodegenerative diseases is the lack of advanced experimental in vitro models that truly mimic the complexity of the human brain. With its ability to emulate microarchitectures and functional characteristics of native organs in vitro, induced pluripotent stem cell technology has enabled the generation of human midbrain organoids. To improve organoid reproducibility and iPSC differentiation, we have developed a sensor-integrated organ-on-a-chip platform allowing long-term cultivation and non-invasive monitoring of hMOs under an interstitial flow regime. Our results show that dynamic cultivation of iPSC-derived hMOs maintains high cellular viabilities and dopaminergic neuron differentiation over prolonged cultivation periods of up to 50 days, while neurotransmitter release of hMOs is detected using an electrochemical sensor array.

11:45

Michael ShulerKeynote Presentation

Body on a Chip: Human Microscale Models for Drug Development
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University, President & CEO, Hesperos, Inc., United States of America

The preclinical drug development process is inefficient at selecting drug candidates for human clinical trials, since only 11% of drug candidates selected for clinical trials exit with regulatory approval. Current technology is based on isolated human cells and animal surrogates.  We believe that a “human” multiorgan model based on physiologically based pharmacokinetics-pharmacodynamic (PBPK-PD) models that house interconnected modules with tissue mimics of various organs.  The system captures key aspects of human physiology that would potentially reduce drug attrition in clinical trials and decrease the cost of development. Integrated, multi-organ microphysiological systems (MPS) based on human tissues (also known as “body-on-a-chip”) could be important tools to improve the selection of drug candidates exiting preclinical trials for those drug most likely to earn regulatory approval from clinical trials. Such microscale systems combine organized human tissues with the techniques of microfabrication.

I will describe such systems being constructed at Hesperos and at Cornell that are guided in their design by a PBPK model. They are “self-contained” in that they can operate independently and do not require external pumps as is the case with man 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. 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 (eg skin, GI tract, blood brain barrier, lung, and kidney). We have achieved unidirectional flow in a pumpless system which is important for mimicking the response of  vascular tissues and constructed blood brain mimics with human in vitro like characteristics. The use of microelectrode arrays to monitor electrically active tissues (cardiac and neuronal) and micro cantilevers (muscle) have been demonstrated. While most systems use 5 or fewer organ modules, we have demonstrated that a 13 “organ” compartment device can be constructed demonstrating the potential to address a wide range of problems in pharmacology and toxicology in a low cost system. Most importantly these technical advances allow prediction of both a drug’s potential efficacy and toxicity (side-effects) in pre-clinical studies.

12:30

Networking Lunch and Round-Table Discussions


Session Title: Organoids and 3D-Culture - Technologies and Applications


Session Chair: Dr. Terry Riss, Promega Corporation

14:00

Recreating Kidney Organogenesis in vitro with Human Pluripotent Stem Cells
Ryuji Morizane, Assistant Professor, Harvard Medical School; Visiting Scholar, Wyss Institute, United States of America

We have developed an efficient, chemically defined protocol for differentiating human pluripotent stem cells into multipotent nephron progenitor cells (NPCs) that can form kidney organoids. By recapitulating metanephric kidney development in vitro we generate SIX2+SALL1+WT1+PAX2+ NPCs with 80-90% efficiency within 8-9 days of differentiation. NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle and distal nephrons in an organized, continuous arrangement that resembles the nephron in vivo. The organoids express genes reflecting many transporters seen in adult metanephric-derived kidney, enabling assessment of transporter-mediated drug nephrotoxicity. Stromal cells are also generated with the presence of PDGFRBeta+ fibroblasts/pericytes, and CD31+ endothelial cells. This kidney differentiation system can be used to study mechanisms of human kidney development. Repetitive injury to tubular cells causes interstitial fibroblast expansion with characteristics of myofibroblasts, indicating kidney organoids can be used to model kidney fibrosis in vitro. Polycystic kidney disease (PKD) patient-derived organoids exhibit cystic phenotypes. Hence the generated kidney organoids are effective tools to study genetic disorders of the kidney as well as mechanisms of kidney injury and fibrosis. Microphysiological platforms in vitro facilitate kidney organoid vascularization and maturation, which may lead to the development of functional bioengineered kidneys in the future.

14:30

Albert FolchKeynote Presentation

Microfluidics For Interrogating Intact Tumor Biopsies
Albert Folch, Professor of Bioengineering, University of Washington, United States of America

The intricate microarchitecture of tissues – the “tissue microenvironment” – is a strong determinant of tissue function. Microfluidics offers an invaluable tool to precisely stimulate, manipulate, and analyze the tissue microenvironment in live tissues and engineer mass transport around and into small tissue volumes. Such control is critical in clinical studies, especially where tissue samples are scarce (e.g. tumor biopsies), in analytical sensors, where testing smaller amounts of analytes results in faster, more portable sensors, and in biological experiments, where accurate control of the cellular microenvironment is needed (e.g. organ-on-a-chip). Microfluidics also provides inexpensive multiplexing strategies to address the pressing need to test large quantities of drugs and reagents on a single biopsy specimen, increasing testing accuracy, relevance, and speed while reducing overall diagnostic cost. I will discuss the development of our platforms for cancer diagnostics that allow for multiplexed functional drug testing on live, intact tissues in various formats: 1) tumor slices; 2) core needle biopsies; and 3) cuboids (precision-sliced tumor fragments that retain viability and the tumor microenvironment for several days). These platforms are currently under commercial development by startup OncoFluidics.

15:00

Ex Vivo Immuno-Oncology Dynamic Environment For Tumor Biopsies
Jeffrey Borenstein, Group Leader, Synthetic Biology, Draper, United States of America

We present the design, construction and testing of a microfluidic perfused tumor microenvironment platform capable of evaluating the efficacy of immune checkpoint inhibitors with circulating immune cells in mouse and human tumor biopsy fragments.

15:30

Afternoo Coffee Break in the Exhibit Hall

16:15

Modeling Immune Mediated Beta Cell Destruction in Human Type 1 Diabetes with Organoids
Matthias von Herrath, Vice President and Senior Medical Officer, Novo Nordisk, Professor, La Jolla Institute, United States of America

In the past 15 years we have been studying the pathology of human type 1 diabetes with access to donor pancreata through the human pancreatic organ donor consortium (nPOD). These studies have led to several findings, for example that certain cytokines are generated by beta cells themselves, sometimes under stress, and also that there are probably key factors that render beta cells susceptible to immune attacks. Mechanistically, the importance and meaning of these observations needs to be addressed in a suitable and easily manipulable in vitro system consisting of human islets and immune cells. We have built such a system in collaboration with the company InSphero and will discuss emerging findings.

16:45

Roger KammKeynote Presentation

Emergent Engineering of Human Neurological Disease Models
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Microphysiological models have now been developed for a variety of single organs, as well as multi-organ systems.  These models are also beginning to find useful applications in the pharmaceutical and biotech industry as disease models and for intermediate throughput drug screening.  The current models range from those that are generated by precisely seeding in a device populations of fully differentiated or primary cells that then assemble into functional monolayers or simple 3D structures on one extreme, to ones that are fully emergent, forming by self-assembly often within a single cluster of pluripotent cells on the other.  We refer to these two approaches as ‘top-down engineering’ and ‘emergent engineering’.  In this presentation, the full range of techniques will be discussed, with examples derived from applications in the context of neurological function and disease.

17:30

Networking Reception with Beer and Wine in the Exhibit Hall -- Meet Exhibitors and Network with Colleagues

18:30

Close


Add to Calendar ▼2020-03-25 00:00:002020-03-25 00:00:00Europe/LondonMulti-Cellular Engineered Living Systems SummitMulti-Cellular Engineered Living Systems Summit in Boston, USABoston, USASELECTBIOenquiries@selectbiosciences.com