iForum Boston

Speakers

From Ideation to Implementation

iForum℠ meetings provide a unique opportunity to connect with thought leaders from academia, government, biotech, and pharma to discover new applications and innovative uses for differentiated iPS cells through interactive, data-driven presentations.

iForum Boston will be held Thursday, September 21 at Harvard Medical School, Boston, MA. Continental breakfast and lunch will be provided on the meeting day along with a networking reception and poster session at the conclusion of the program.

During this premier stem cell event, key opinion leaders will share their insights, investigations, and future plans for utilizing iPS cells in experimental designs. Featured topics will include complex models and regenerative medicine, disease modeling and drug discovery, and predictive toxicology.

Confirmed Speakers

  • Keynote: Donald E. Ingber, MD, PhD, Director, Wyss Institute for Biologically Inspired Engineering at Harvard University, Judah Folkman Professor of Vascular Biology, Harvard Medical School & Vascular Biology Program, Boston Children’s Hospital, Professor of Bioengineering, Harvard John A. Paulson School of Engineering and Applied Sciences
  • Edsel Abud, PhD, MD/PhD Student, UC – Irvine School of Medicine
  • Lowry Curley, PhD, CEO, AxoSim Technologies
  • Victor Hernandez-Gordillo, PhD, Postdoctoral Associate, Massachusetts Institute of Technology
  • J. Eric McDuffie, PhD, Scientific Director, Head, Mechanistic & Investigative Toxicology (MIT), Janssen Research & Development, LLC
  • Leonard Kaczmarek, PhD, Professor of Pharmacology and of Cellular And Molecular Physiology, Yale University
  • Bjorn Knollmann, MD, PhD, Professor of Pharmacology and Medicine, Vanderbilt University
  • Bruce Novich, PhD, Chief Business Officer, Executive Vice President and General Manager, Cellular Dynamics International Corporation. a FUJIIFILM Company
  • Jennifer Smith, PhD, Co-founder, Chief Scientific Officer, PreCyte Inc.
  • Hao Wu, PhD, Senior Scientist, Fulcrum Therapeutics

Agenda


9:00 am |

Breakfast, Poster Setup

A continental breakfast will be served in the ground floor of the Joseph B. Martin Conference Center.
Poster presenters: Please set up your posters prior to 10:00 am.

10:00 am |

Welcome - Bruce Novich, Cellular Dynamics International

Bruce Novich, PhD
Executive Vice President and General Manager
Cellular Dynamics International - A Fujifilm Company

10:15 am |

Keynote: Human Organs-on-Chips
Donald E. Ingber, MD, PhD, Harvard University

Donald E. Ingber, MD, PhD
Director, Wyss Institute for Biologically Inspired Engineering at Harvard University
Judah Folkman Professor of Vascular Biology,
Harvard Medical School & Vascular Biology Program,
Boston Children’s Hospital
Professor of Bioengineering, Harvard John A. Paulson School of Engineering and Applied Sciences

Abstract: At the Wyss Institute for Biologically Inspired Engineering at Harvard University that I lead, we seek to develop innovative technologies that will transform medicine and the environment by emulating the way nature builds. One of the biggest problems in medicine today is that the drug development model is broken. Even though financial investment in research and drug discovery has increased dramatically over the past few decades, the number of medicines approved per dollar investment has steadily decreased over the past 50 years. A major limiting factor is that animal models remain at the core of drug testing and development even though they are costly, time-consuming, lead to loss of innumerable animal lives, and often fail to predict results in humans.

In this presentation, I will describe work we have been carrying out in the Biomimetic Microsystems platform at the Wyss Institute, which is focused specifically on developing a solution to this problem. The goal of the platform is to engineer human ‘Organs-on-Chips’: microdevices lined by living human cells created with computer microchip manufacturing techniques that recapitulate organ-level functions as a way to replace animal testing. We started by defining the biological design principles that govern the structure and hysiological function of a key functional unit of a living human lung: the air sac or  lveolus that is the site of gas exchange, aerosol-based drug delivery, inhalation of airborne articulates, pneumonia, etc. The air sac is composed of a single layer of epithelial cells that line the air sac, which form an interface with underlying layer of blood vessel endothelial cells, separated by a planar porous extracellular matrix adhesion scaffold. The function of the lung also requires mechanical breathing motions and fluid flow in the vascular system. Inspired by these design principles, we used computer chip manufacturing methods to microfabricate a synthetic human lung air sac. The engineered human lung-on-a-chip is a crystal clear, flexible rubber device about the size of a memory stick that contains three, tiny hollow channels oriented in parallel. The top and bottom parts of the central channel are separated by a thin, flexible, porous membrane that is coated with extracellular matrix and lined on one side with human lung air sac cells and exposed to air; human lung capillary blood cells are placed on the other side with medium containing human immune cells flowing over their surface to mimic blood. A vacuum applied to the two outer side channels deforms this tissue-tissue interface to recreate the way lung tissues physically expand and retract when breathing in the whole human lung. Studies carried out with this device have provided the proof-of-principle that an organ-on-a-chip can be used to identify drug toxicities, discover new potential therapeutic agents, and model complex human diseases such as pulmonary edema (‘fluid-on-the-lungs’) in vitro.

I will review our work on the lung chip as well as recent advances we have made in the development of many other human organ chips, including small airway, gut, kidney, liver and bone marrow chips, as well as novel human disease and infection models. I will also describe our ongoing efforts to develop a ‘human body on chips’ composed of more than 10 different human organ chips linked together by fluid flowing through their vascular channels, and to engineer an automated instrument for real-time analysis of cellular responses to pharmaceuticals, toxins, cosmetics and other chemicals using these bioinspired devices.

10:50 am |

Human iPSC-derived Microglia to Study Alzheimer's Disease Genetics
Edsel Abud - University of California, Irvine

Edsel Abud, PhD
University of California
Irvine School of Medicine
Irvine, CA

11:15 am |

Refreshments (provided), Poster Session

Refreshments and the poster session will take place in the ground floor lobby.

11:45 am |

Modeling Fragile X Syndrome in vitro and in vivo using iPS cell technology
Hao Wu, Fulcrum Therapeutics

Hao Wu, PhD
Senior Scientist
Fulcrum Therapeutics

12:10 pm |

Assessment of Excitotoxicity Risk using Human iPSC-derived Glutamatergic Neurons
J. Eric McDuffie, Janssen

J. Eric McDuffie, PhD

Scientific Director
Janssen Pharmaceuticals
San Diego, CA

Abstract
Our aim was to validate human induced pluripotent stem cell (hiPSC)-derived GlutaNeurons and Glutamatergic Neuron-Astrocyte Co-Cultures to predict glutamate excitotoxicity for de-risking discovery compounds. We assessed concentration- and time dependent effects of glutamate receptor agonists and antagonists and a fatty acid amide hydrolase (FAAH) inhibitor on glutamate (GLU) excitotoxicity. Kainate (KA, positive control) reduced cell viability in both GlutaNeurons and Glutamatergic Neuron-Astrocyte Co-cultures. GLU reduced GlutaNeuron viability which was partially attenuated by the NMDA receptor antagonist, MK801. GLU induced excitatory responses were not evident in the Neuron Astrocyte Co cultures, indicating GLU glutamine cycling. KA induced reduction in Glutamatergic Neuron-Astrocyte Co culture viability was partially attenuated, while that induced by AMPA was completely blocked by AMPA/KA receptor antagonist, NBQX. Both KA and GLU increased synaptic activity in GlutaNeurons. MK801 attenuated the excitation induced by GLU. No GLU induced changes in synaptic activity were detected from Glutamatergic Neuron-Astrocyte Co-cultures. URB597 reduced GLU-induced excitation. Our findings highlight the utility of neuronal models to de-risk potentially translatable neurotoxicity.

12:35 pm |

Lunch (provided), Poster Session

Lunch and the poster session will take place in the ground floor lobby.

1:35 pm |

An Indicator Cell Assay for Blood-based Diagnostics
Jennifer Smith, PreCyte

Jennifer Smith, PhD
Chief Scientific Officer
PreCyte Inc.

Abstract: PreCyte is developing the Indicator Cell Assay Platform (iCAP), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients’ blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, disease classifiers based on a small number of features. We are developing iCAP assays for pre-symptomatic and early symptomatic detection of amyotrophic lateral sclerosis and Alzheimer’s disease.

2:00 pm |

Human Motor-Nerve-On-A-Chip for Predictive Preclinical Testing
Lowry Curley, AxoSim

Lowry Curley
Chief Executive Officer
AxoSim Technologies, LLC

Abstract:
Motor neuron diseases are progressive neurodegenerative disease responsible for the death of both upper and/or lower motor neurons resulting in symptoms such as spasticity, rigidity, and atrophy of muscles. Amyotrophic Lateral Sclerosis (ALS), a kind of motor neuron disease, alone affects about 6,000 people every year in the United States with average life expectancy of 2-5 years. Due to the complexity and relative inaccessibility of the nervous system and lack of availability of human neuronal cells, preclinical testing for drugs is largely performed on animal models. With the advent of induced pluripotent stem cells (iPSC) technology, it is now possible to develop high throughput disease-specific in vitro tests to screen a variety of compounds of interest. While these 2D in vitro tests provides information about many valuable parameters such as neurite length and cytotoxicity, they still lack information about clinically relevant parameters such as compound action potential and myelination. AxoSim invented a 3D microengineered Human-Motor-Nerve-On-A-Chip system whose structure and physiology resemble native peripheral nerve tissues. We successfully incorporated iPSCs derived motor neurons, astrocytes, and primary Schwann cells to create a model with defined architecture and robust neurite outgrowth (>4mm). We envision that this invention will revolutionize the field of preclinical neurotoxicity testing in terms of efficiency, cost, and clinical applicability.

2:25 pm |

The Use of iPS Cells in Neurological Disorders
Leonard Kaczmarek, Yale School of Medicine

Leonard  Kaczmarek, PhD
Professor of Pharmacology and of Cellular And Molecular Physiology Biography
Yale School of Medicine

Abstract:
The presentation will cover the use of neurons derived from iPS cells in the investigation of two different genetic conditions. The first is Spinocerebellar Ataxia type 13, which is caused by mutations in the gene for Kv3.3, a voltage-dependent potassium channel that is expressed at high levels in Purkinje cells of the cerebellum and in auditory brainstem nuclei. The second set of human mutations discussed are those that alter the activity of the KCNT1 potassium channel, also known as the Slack channel. Mutations in this channel give rise to several types of early-onset epilepsies, including Malignant Migrating Partial Seizures in Infancy, Autosomal Dominant Frontal Lobe Epilepsy and Ohtahara Syndrome. Each of these is associated with very severe intellectual disability. The use of iPS cells in these disorders has been key to establishing the biological consequences of the mutations and validating the therapeutic approaches that are now underway.

2:50 pm |

Refreshments (provided), Poster Session

Refreshments and the poster session will take place in the ground floor lobby.

3:20 pm |

Bioengineering the Intestinal Stem Cell Niche
Victor Hernandez-Gordillo, PhD, MIT

Victor Hernandez-Gordillo, PhD
Postdoctoral Associate
Massachusetts Institute of Technology

Abstract: Intestinal organoids have gained relevance as a tool in preclinical drug discovery, disease modeling and basic stem cell research. For instance, forskolin-induced swelling is currently used to asses drug response in organoids derived from Cystic Fibrosis patients. Similarly, intestinal organoids have been used to investigate intestinal wound repair upon prostaglandin E2 (PGE2) stimulation. Matrigel hydrogels in combination with 3 key signaling proteins; Wnt-3A, R-spondin, and Noggin, are the predominant intestinal organoid culture medium used in drug discovery. However, Matrigel is ill-defined, varies from lot to lot, and contains numerous bioactive soluble proteins (EGF, VEGF, IGFB-1, etc) that could affect drug response. Exactly how these soluble factors could impact drug discovery (either synergist or antagonist with the test drug) is unknown. Further complexity arises when using conditioned medium that introduces high concentration of FBS (up to 20%). During the talk I will be presenting strategies for the rational design of a biocompatible and fully-defined synthetic matrix to culture post-natal intestinal stem cells. Further I will discuss how we are using these fully-defined synthetic matrices in drug discovery.

3:45 pm |

Modeling Heart Disease with Human iPSC-derived Cardiomyocytes: First Experiences with CardioExcyte96
Bjorn Knollmann, Vanderbilt University

Bjorn Knollmann, MD, PhD
Professor of Medicine
Vanderbilt University
Nashville, TN

Abstract:
Academically generated human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CM) has revolutionized our ability to model heart disease. Coupled with recent gene editing techniques, we are now able to generate isogenic controls from cells of patients with disease resulting in a powerful tool for cardiomyocyte specific mechanisms of disease pathogenesis. Current gold standard techniques for the investigation of cellular contractility and electrophysiological activity has relied primarily on single cell assessment using edge detection via the IonOptix system and patch clamp respectively. However, to assess the pathogenicity of novel mutations better methods are needed for screening disease outcomes before moving to single cell analyses. Using academically-generated HCM, DCM and LQT iPSC models, we report our first experiences comparing the relationship between gold standard techniques for measuring single cell contractility and electrophysiological based parameters to high-throughput impedance and extracellular field potential (EFP) measurements from monolayers with the CardioExcyte96 (Nanion) system. Day 30 hiPSC-CM generated using standard chemical differentiation methods were utilized for the following techniques. For single cell assessment of contractility and action potentials, d30 cells were plated on flexible Matrigel substrate and allowed to mature for 5 days prior to edge detection assessment of Fura2 loaded cells using IonOptix and patch clamp.

4:10 - 6:00 pm |

Poster & Exhibits Networking

Please join us for a networking reception with heavy hors d'oeuvres and cocktails in the ground floor lobby.


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Poster Presentations

Poster Presentations

Phenotyping of Human iPSC-derived Dopaminergic Neurons Containing the Engineered A53T α-Synuclein Mutation

Sabine Lange, Kwi Hye Kim, Kile Mangan, Eugenia Jones, Sarah Dickerson, Tom Burke, Lauren Little, Lucas Chase, Brad Swanson, and Coby Carlson

Cellular Dynamics International, a FUJIFILM Company


Evaluating Networked Activity as an Integrated Assay for Seizurogenic Assessment Using Stem Cell Derived Glutamatergic Neurons

Kwi Hye Kim, Coby Carlson, Christian Kannemeier, Tromondae K Feaster, Brad Swanson, Blake D Anson and Kile Mangan

Cellular Dynamics International, a FUJIFILM Company


Modeling Liver Disease Using Human iPSC-derived Hepatocytes

Michael Hancock, Victoria Echeverria and David Mann

Cellular Dynamics International, a FUJIFILM Company


Human iPS-derived Motor Neurons Harboring TDP-43 Mutations: Applications and Possibilities

B Freitas, K.H. Kim, R. Lhanas, J. Liu, B. Meline, C. Chavez, C. McMahon, W.B. Wang, D. Mann and E. Jones

Cellular Dynamics International, a FUJIFILM Company


Disease Modeling of Hypertrophic Cardiomyopathy Using Human iPSC-derived Cardiomyocytes

Sabine Lange, Natsuyo Aoyama, Jun Wang, Rebecca Fiene, and Coby Carlson

Cellular Dynamics International, a FUJIFILM Company

Sponsors

iForum Boston Sponsors

 


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