The ISSCR Annual Meeting sits at the heart of stem cell and regenerative medicine, where scientists connect globally. Engage with the latest science and technologies, and envision new possibilities for your research.
The meeting will take place 20-23 June, 2018 at the Melbourne Convention and Exhibition Centre, located on the banks of the Yarra River and surrounded by bustling restaurants, bars, shops and attractions.
Come visit FUJIFILM Cellular Dynamics at Booth #97
Join Us for an Innovation Showcase
Thursday, Jun 21 | 11:30 – 12:30pm | Room 106, Level 1
Novel Applications of Human iPSC-derived Neurons: From High-throughput Screening to Patch-seq Analysis
Presented By: FUJIFILM Cellular Dynamics, Inc.
Speakers: Anne Bang, Director, Cell Biology, Sanford Burnham Prebys Medical Discovery Institute and Cedric Bardy, Assistant Professor – South Australian Health and Medical Research Institute (SAHMRI Mind & Brain)
Part I: Dr. Anne Bang will discuss the use of hiPSC-derived neurons, including iCell® GABANeurons and iCell DopaNeurons, in high-throughput assays for phenotypic analyses and drug screening. She will describe the development of a suite of foundational assays in higher throughput formats to monitor neuronal morphology, mitochondrial function, and electrophysiology, and address the challenges of balancing higher throughput with relevance.
Part II: Dr. Cedric Bardy will discuss patch-seq characterization of hiPSC-derived neurons with electrophysiology, morphological analysis and single-cell RNAseq. The integration of single-cell electrophysiology, morphology and transcriptomics analysis of live human neural cells enables a bridging of human neurophysiology with gene expression. This novel approach allows the identification of neurons in specific functional states and can compensate for variations among cell lines.
Poster: W-4055 | Wednesday, Jun 20 | 6:30 – 7:30pm
The Generation and Functional Characterization of Human Microglia from Episomally Reprogrammed iCell® Hematopoietic Progenitor Cells
Authors: Eugenia Jones, Deepika Rajesh, Sarah Burton, Christie Munn, Michael Hancock, Kwi Hye Kim, Simon Hilcove, and Tom Burke
FUJIFILM Cellular Dynamics, Inc.
Abstract: Microglia maintain immunological balance within the central nervous system by decreasing inflammation due to injury and buildup of cytotoxic substances and infectious material. Microglia research has been largely confined to rodents because human primary microglia are difficult to acquire and stably maintain in culture conditions. Here, we describe the generation, functional characterization and cryopreservation of human induced pluripotent stem cell-derived microglia (iMGL) from episomally reprogrammed iCell® Hematopoietic Progenitor Cells (proprietary technology) under defined conditions based on technology developed by the Blurton-Jones laboratory exclusively licensed to FCDI from the University of California-Irvine. iMGL retain purity, secrete immunomodulatory cytokines and phagocytose pHrodo-labelled bacterial bioparticles and amyloid beta (Aβ) fibrils. The ability to produce essentially limitless quantities of iMGL holds great promise for accelerating human neuroscience research into the role of microglia in normal and diseased states.
Poster: W-4056 | Wednesday, Jun 20 | 7:30 – 8:30pm
Human iPSC-derived Motor Neurons: Coculture with Skeletal Myoblasts and Investigating TDP-43 Mutations
Authors: Simon Hilcove1, Beatriz Freitas1, Lauren Fong2, Jeanie Liu1, Ben Maline1, Carrie Chavez1, Chris McMahon1, Wen Bo Wang1, Dave Mann1, Jamshid Arjomand2, Uli Schmidt2, Eugenia Jones1
- FUJIFILM Cellular Dynamics, Inc.
- Genea Biocells US Inc.
Abstract: The ability to produce motor neurons from induced pluripotent stem cells (iPSCs) provides the means to model several neuromuscular disorders using human cells. It is now possible to explore human-specific drug screening platforms with prospective treatment possibilities using iPS-derived motor neurons for disorders lacking therapeutic options such as amyotrophic lateral sclerosis (ALS). Here we demonstrate the generation of iPSC-derived motor neurons using an optimized differentiation protocol generating a population with greater than 60% purity based on Isl1/2 and Tuj1 positive staining. Furthermore, we used this cell line to generate a TDP-43 line, equipping researchers with this valuable tool for ALS prognostics and treatment. We characterize our cells and cocultured them with human skeletal muscle, capable of forming neuromuscular junctions in vitro. We are now exploring co-culture conditions with human iPSC-derived skeletal muscle based on our published protocol (Caron et al. 2016). Our media-based differentiation method efficiently generates contractile and fused myotubes without the need for any cell sorting or myogenic gene overexpression. Combined with our motor neurons, this coculture platform will enable ALS drug discovery and facilitate complex disease modeling of other neuromuscular disorders.
Poster: T-4055 | Thursday, Jun 21 | 6:00 – 7:00pm
Evaluation of Hypertrophic Cardiomyopathy Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes Reveals Abnormal Excitation Contraction Coupling
Authors: Simon Hilcove, Natsuyo Aoyama, Jing Liu, Souameng Lor, Katherine Czysz, Tromondae Feaster, and Eugenia Jones
FUJIFILM Cellular Dynamics, Inc.
Abstract: Sarcomeric cardiomyopathies, including hypertrophic cardiomyopathy (HCM), are an important cause of morbidity and mortality. Clinically, HCM is characterized by ventricular wall thickening as a result of enlarged cardiomyocytes, preserved ejection fraction concurrent with diastolic dysfunction, and arrhythmias. One of the most common forms of HCM arises from a missense mutation in the gene encoding the beta myosin heavy chain protein (MYH7), resulting in a change of amino acid 403 from arginine-to-glycine (R403Q). However, the pathobiology of this mutation remains generally poorly understood. A major hindrance to detailed study of sarcomeric cardiomyopathies in humans has been lack of an appropriate in vitro cardiac tissue model. Here, we use human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) to study the functional consequence of the HCM MYH7 R403Q mutation, specifically electrophysiology, calcium handling, and contraction. HiPSC-CMs were generated through reprogramming of somatic cells from a patient carrying the HCM MYH7 R403Q mutation. In addition, we use genome engineering strategies to correct the mutation, creating an isogenic control. Moreover, we developed an induced hypertrophy model by exposing control hiPSC-CMs to endothelin-1 (ET-1). Both inherited and induced models display classic hallmarks of hypertrophy, including up-regulation of fetal genes, cytoskeletal rearrangements, and increased hiPSC-CM size. In addition, the HCM MYH7 R403Q hiPSC-CMs display abnormal electrophysiological properties and calcium handling properties including significantly slower calcium decay rates and prolonged calcium handling kinetics (i.e., time to peak and time to baseline) concurrent with contractile dysfunction. These data illustrate the advantages of disease modeling using hiPSC technology. We conclude that patient-specific hiPSC-CMs exhibit classic clinical phenotypes relative to control. We show that the induced and inherited HCM phenotype hiPSC-CMs have common structural and functional features. In total, hiPSC technology enables a reliable and reproducible disease model not previously attainable and provides new solutions, tools, and opportunities for sarcomeric cardiomyopathy mechanistic elucidation and novel therapeutic research.
Electrophysiological Phentype Characterization of Human iPSC-derived Dopaminergic Neuronal Lines by Means of High-resolution Microelectrode Arrays
Authors: Michele Fiscella1, Noelle Leary2, Silvia Ronchi2, Andreas Hierlemann2
- ETH Zurich / MaxWell Biosystems AG, Basel, Switzerland
- ETH Zurich, Basel, Switzerland
Detailed Characterization of iPSC Lines and iPSC-derived Motor Neurons Harboring a 1.35MB Complex Insertion
Authors: Anthony N. Cutrupi1, Gonzalo Perez-Siles2, Megan Brewer2, Renata de Moraes Maciel3, Garth Nicholoson1, Mario Saporta3, Marina Kennerson2
- University of Sydney, Sydney, New South Wales, Australia
- ANZAC Reserach Institute, Sydney, New South Wales, Australia
- University of Miami, Miller School of Medicine, Miami, FL, U.S.
High-content Assay for Morphological Characterization of 3D Neuronal Networks in an Organ-on-a-Chip Microfluidic Platform
Authors: Oksana Sirenko1, Remko van Vught2, Chiwan Chiang2, Karlijn Wilschut2, Grischa Chandy1, Penny Travomina1, Michael Hancock3, Jos Joore2, Paul Vulto2
- Molecular Devices LLC, San Jose, CA, U.S.
- MIMETAS, Leiden, Netherlands
- FUJIFILM Cellular Dynamics, Inc.