Events

Loading Events

« All Events

  • This event has passed.

ISSCR 2016 Annual Meeting

June 22, 2016 - June 25, 2016

Event Navigation

At the heart of stem cell science is the ISSCR Annual Meeting – a place were great science, collaboration, and research across the breadth of the field come together to turn the promise of our field into scientific progress that will change the face of human health. This is the meeting that lets you take control of your experience and what you’ll discover.

Learn more about Cellular Dynamics at these ISSCR activities:

Wednesday, Jun 22

Talk | Wed, Jun 22 | 11:30 - 11:50 am | Rooms 2014 - 2018
Functional Analysis of iPSC-derived Cardiomyocytes to Understand Cardiac Disease Mechanisms

Session: Humanity in a Dish: Functional Analysis of iPSC-derived Cardiomyocytes to Understand Cardiac Disease Mechanisms | 9:00 am – 12:30 pm | Rooms 2014 – 2018

Speaker: Ulrich Broeckel MD, Medical College of Wisconsin

Abstract: Cardiomyocytes derived from patient specific iPSCs offer an unprecedented platform to understand and model complex disease mechanisms. We selected a subset of individuals from a large bi‐racial epidemiological study, the NHLBI HyperGen cohort and developed iPSC derived cardiomyocytes. We discuss our approach to model cell type specific functional changes associated with the development of Left Ventricular Hypertrophy, a common and independent risk factor for cardiovascular disease. These analyses provide novel insights into gene regulation and direct towards the development of novel disease biomarkers.

Poster W2101 | Wed, Jun 22 | 6:30 pm
GMP-compatible iPSC Derivation from Human Umbilical Cord Blood and Tissue across Multiple Donors

Presenter: Amanda Mack, PhD, Cellular Dynamics International

Authors: Amanda Mack, PhD1, Elizabeth Faust1, Kevin Monroe1, Ryan Wachowiak, MS1, Wen Bo Wang, PhD1, Katherine Brown, PhD2, Matthew Skiles, PhD2, and Heather Brown, MS2

1 Cellular Dynamics International, a Fujifilm company, Madison, WI, USA
2 CBR Systems Inc, San Bruno, CA, USA

Abstract: Induced pluripotent stem cells (iPSCs) can be generated from newborn tissues stored in one of the world’s largest cord blood banks, Cord Blood Registry®, using an integration-free, clinically applicable reprograming method. We demonstrate the ability to generate iPSCs from umbilical cord blood units processed manually using a Ficoll gradient or on the fully automated AutoXpress® (AXP) platform (Cesca Therapeutics). AXP and Ficoll processed cord blood units were cryopreserved for up to 5 and 10 years respectively. Resulting iPSCs exhibit characteristic gene expression profiling, do not contain residual reprogramming factors, are normal in karyotype, and match the identity of the original starting material. This study also compares reprogramming capacity of cord blood and mesenchymal stem cells isolated from thawed umbilical cord tissue, previously cryopreserved as a composite material, from the same donor. Furthermore, we demonstrate that less than 1 million cells can be used as starting material for iPSC derivation making for a tractable system when tissue amounts and types are limited. This study serves as a proof of principle that stem cells from multiple newborn tissues cryopreserved at a cord blood bank can be used as starting material for iPSC reprogramming under conditions compatible for subsequent transition to a GMP facility for clinical applications.

Thursday, Jun 23

Poster T1069 | Thu, Jun 23 | 6:00 pm
Multi-parametric Assessment of Drug Effects on Cardiomyocyte Physiology Using iPSC Derived Cardiac Spheroids

Presenter: Jayne Hesley, PhD, Molecular Devices

Authors: Oksana Sirenko1, Coby B Carlson2, David Mann2, Michael Hancock2, Steve Luke1, Anish Seshadri1, Jayne Hesley1, Evan Cromwell3, and Jason Gentry1

1 Molecular Devices, Sunnyvale, CA, USA
2 Cellular Dynamics International, a Fujifilm company, Madison, WI, USA
3 Protein Fluidics, Hayward, CA, USA

Abstract: Cell models are becoming more complex in order to better mimic the in vivo environment and provide greater predictivity for compound efficacy and toxicity. There is an increasing interest in using three-dimensional (3D) organoids for modelling developmental and tissue biology with the goal of accelerating translation research in these areas. These 3D in vitro models span the gap between two-dimensional cell cultures and whole-animal systems and can provide unique perspectives on the behavior of stem cells and developing tissues and organs. However, challenges remain with extracting information from these models. Accordingly, development of quantitative higher throughput assays in 3D cultures is an active area of investigation. We developed methods for the forming of cardiac organoids derived from the human iPSC and measuring the impact of drug candidates on the beating rate of cardiac organoids using high content and fast kinetic fluorescence imaging. Cardiomyocyte contraction rate and pattern are characterized by monitoring changes in intracellular Ca2+ measured using calcium sensitive dyes. The impact on cell viability and mitochondria integrity was evaluated by high content imaging. The assay was optimized for HTS and allows characterization of beating profiles by using multi-parameter analysis outputs such as beating rate, peak frequency and width, or waveform irregularities. Next, we tested known cardioactive and cardiotoxic compounds including a and b blockers, hERG inhibitors, ion channel blockers, as well as selected environmental toxins (pesticides, flame retardants, and polycyclic aromatic hydrocarbons). We compared IC50 values for the 3D versus 2D models and demonstrated significant differences in the assay sensitivity to compound effects. The assay was further characterized using commercially available cardiotoxicity library representing different classes of compounds including receptor antagonists, ion channel blockers, anti-cancer and anti-inflammatory drugs, and kinase inhibitors. We conclude that the assay is suitable for the high throughput screening and shows utility for screening compounds in 3D models for potential to cause cardiotoxicity.

Friday, Jun 24

Meet-up Hub | Fri, Jun 24 | 12:15 - 1:00 pm
The CIRM iPSC Collection at Coriell

Speakers/hosts: CIRM, Coriell Institute, and Cellular Dynamics International

Poster F2125 | Fri, Jun 24 | 6:00 pm
Novel iPSC-derived Cellular Systems for In Vitro Disease Modeling

Presenter: Coby Carlson, PhD, Cellular Dynamics International

Authors: Coby B Carlson, Blake Anson, Susan DeLaura, David Mann, and Eugenia Jones
Cellular Dynamics International, a Fujifilm company, Madison, WI, USA

Abstract: A major challenge in drug discovery research is modeling human biology in an in vitro system that is both physiologically relevant and predictive of the disease state. Human induced pluripotent stem cell (iPSC) technology allows for the generation of unlimited quantities of virtually any cell type in the human body from numerous donors. This technology also enables access to human disease models which have been shown to recapitulate the native phenotype in vitro. The functional relevance of human iPSC-derived cell types in research and drug discovery programs is being demonstrated by a rapidly growing body of literature. Here, we present case study examples of induced, engineered, and innate disease models generated by the production of iPSC-derived cell types environmentally stimulated to elicit a disease phenotype, genetically modified to introduce a disease mutation, or from patient-derived material, respectively.

In particular, we describe the application of iPSC-derived hepatocytes in hepatitis C virus (HCV) infectivity. We present an induced model of Alzheimer’s disease (AD) where beta-amyloid-dependent toxicity is induced in iPSC-derived cortical neurons. This assay was developed for a pilot screen to identify compounds protective against AD. We also provide data from iPSC lines genetically modified to carry point mutations in the amyloid precursor protein yielding another neuron-based Alzheimer’s model. Finally, we showcase an iPSC-derived diabetic cardiomyopathy model, in which culture conditions were optimized to induce the disease state in apparently normal iPSC-derived cardiomyocytes. This model was used in a phenotypic screen for rescue from the pathological phenotype during diabetic stress and identified candidate molecules that were subsequently shown to be protective in cardiomyocytes derived from diabetic patient-specific iPS cell lines. Overall, these illustrate how iPSC technology offers reliable and predictive model systems not otherwise attainable using currently available primary and immortalized cells, thus creating new tools and opportunities in drug discovery.

Poster F2126 | Fri, Jun 24 | 6:00 pm
Accessing Population Biology through Large Scale Generation of Human iPSCs from Disease Cohorts

Presenter: Eugenia Jones, PhD, Cellular Dynamics International

Authors: Eugenia Jones1, Amanda Mack1, Thomas Novak2, Ulrich Broeckel3, Christopher McMahon1, and Thomas J Burke1

1 Cellular Dynamics International, a Fujifilm company, Madison, WI, USA
2 Cellular Dynamics International, a Fujifilm company, Novato, CA, USA
3 Medical College of Wisconsin, Milwaukee, WI, USA

Abstract: Induced pluripotent stem cell (iPSC) technology brings undisputed value to understanding disease pathology and therapeutic intervention/prevention. Large scale reprogramming efforts are building on this value by moving from individual examples of iPSC-based disease recapitulations to population-based investigations. Cellular Dynamics International (CDI) has pioneered these efforts by developing processes to generate iPSC lines from over 3200 donors from control and disease cohorts through the initiatives of the US-National Heart, Lung, Blood Institute (NHLBI) and The California Institute of Regenerative Medicine (CIRM).

The industrialized processes developed at CDI are meeting the demands of these initiatives where, to date over 1150 samples have been reprogrammed collectively from both programs with the remaining ~2100 samples from CIRM on schedule to be reprogrammed before the end of the initiative (December 2016).

The first 300 iPSC lines from the CIRM effort have been deposited into the Coriell Institute as of September 1, 2015 and the iPSCs from the NHLBI initiative will be deposited into WiCell Research Institute. Both repositories will provide iPSCs and links to varying degrees of relevant descriptive and clinical information.
In addition to reprogramming and banking, CDI has also generated cardiomyocytes from over 230 of the NHLBl-sourced donors for use with in vitro investigations.

Ultimately, the lessons learned from these large scale reprogramming and differentiation efforts and the availability of the iPSC material will aid in future population-based reprogramming efforts, investigations of disease etiology, and potential therapies.

Poster F2131 | Fri, Jun 24 | 6:00 pm
Development and Functional Applications of Human iPSC-derived Spinal Motor Neurons

Presenter: Carrie Chavez, PhD, Cellular Dynamics International

Authors: Carrie Chavez, Benjamin Meline, Jing Liu, Michael McLachlan, Thomas Burke, Eugenia Jones, Christopher McMahon, and Wen Bo Wang
Cellular Dynamics International, a Fujifilm company, Madison, WI, USA

Abstract: The aim of this study was to produce spinal motor neurons from human induced pluripotent stem cells (iPSCs) with sufficient purity for use in a multitude of downstream assays including electrophysiological recordings using a multi-electrode array (MEA) system. In particular we wanted to produce motor neurons that could be cultured in defined conditions over long periods of time, without being hampered by outgrowth from proliferative cell types. Using an optimized 3D differentiation protocol that improves upon published methods, we were able to produce motor neurons from iPSCs at greater than 60% purity as measured by Isl 1/2 and Tuj1 positive staining. These cells can be stored frozen, thawed, and cultured in media without glia for extended periods, simplifying experimental design and data interpretation. We collected ICC, qPCR and MEA data to characterize the motor neuron cells and used iPSC lines from multiple donors to demonstrate a robust protocol that produces motor neurons independent of donor iPSC line. In addition, genetically modified iPSC lines were generated to create an isogenic disease model for Amyotrophic Lateral Sclerosis. These data show the characteristics and utilization of motor neurons produced from iPSC.

Poster F3063 | Fri, Jun 24 | 6:00 pm
Cryopreserved Midbrain Dopamine Neurons Derived from Human iPSC Reverse Behavioral Deficits in Parkinsonian Animals

Presenter: Dustin Wakeman, PhD, Rush University

Authors: Dustin R Wakeman1, Benjamin M Hiller1, David J Marmion1, Christopher W McMahon2, Junyi Ma2, Grant T Corbett1, and Jeffrey H Kordower1

1 Rush University, Chicago, IL, USA,
2 Cellular Dynamics International, a Fujifilm company, Madison, WI, USA

Abstract: Large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation is a major hurdle for clinical translation of pluripotent stem cell based therapies for neurodegenerative disorders like Parkinson’s disease. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) via floor plate induction and cryopreserved in large production lots for biochemical screening and transplantation studies. Upon thaw, cryopreserved iPSC-mDA neurons retained high viability with a gene expression profile similar to the human substantia nigra. Biochemical analysis confirmed a protein expression signature consistent with the midbrain floor-plate lineage. In addition, iPSC-mDAs released dopamine upon depolarization with KCl stimulation. Furthermore, electrophysiological recordings revealed firing of both spontaneous and evoked action potentials with active Na+ and K+ channels responsive to pharmaceutical inhibition. In order to test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without sub-culturing into the 6-OHDA-lesioned rat and MPTP-non-human-primate models of Parkinson’s disease. Grafted neurons demonstrated robust survival, extensive fiber outgrowth, and innervation of host parenchyma in both rodent (1-month) and macaque (3-months). Immunohistochemistry of grafted neurons confirmed co-expression of human midbrain lineage, A9 subtype dopamine neuron markers (FoxA2, TH, Girk2, human-Nuclei, and human-NCAM). Furthermore, a behavioral study in 6-OHDA-lesioned parkinsonian rats revealed statistically significant reversal in functional deficits in both amphetamine and apomorphine induced rotational asymmetry for up to 6-months post-transplantation with complete iPSC-mDA neuron graft reinnervation of the host striatum. Critically for safety, no proliferation in transplanted cells was observed by Ki-67 staining at any time points tested in the 6-OHDA-lesioned rat or MPTP-macaque. The results demonstrate excellent graft survival, maintenance of the midbrain dopaminergic phenotype, and lack of neural overgrowth in parkinsonian rats and monkeys, as well as indicate considerable promise for the development of pluripotent cell-based therapies in PD.

Saturday, Jun 24

Talk | Sat, Jun 25 | 2:15 - 2:30 pm
CIRM's Human Induced Pluripotent Stem Cell Bank at the Coriell Institute: The World's Largest Public Collection of Pluripotent Stem Cells for the Understanding and Treatment of Complex Genetic Diseases

Presenter: Cristian A Perez, PhD, Coriell Institute for Medical Research

Authors: Cristian A Perez1, Daniel Huber1, Julia Hand1, Matthew Tenorio1, Stephen Lin2, Thomas Novak3, and Andrew MacKnight1

1 Coriell Institute for Medical Research, Camden, NJ, USA
2 California Institute for Regenerative Medicine, San Francisco, CA, USA
3 Cellular Dynamics International, a Fujifilm company, Novato, CA, USA

Abstract: Induced pluripotent stem cells (iPSCs) reprogrammed from patient-derived skin or blood cells have become a key resource for human disease modeling and therapy discovery and development. The California Institute for Regenerative Medicine (CIRM) recognized the value and need for these resources and created the CIRM Human Induced Pluripotent Stem Cell Bank.

To ensure the proper storage, handling, and distribution of these samples CIRM partnered with the Coriell Institute for Medical Research, a leader in biobanking management. With a satellite location in Novato, California, Coriell provides clinical data management, data hosting, and biospecimen storage and distribution services.

The CIRM hiPSC Bank includes a range of genetically complex diseases: Alzheimer’s disease, Blinding Eye Diseases, Cardiomyopathies, Fatty Liver Disease, Hepatitis C, IPF, Autism Spectrum, Cerebral Palsy, Epilepsy, and also normal controls. These iPSCs are produced by Cellular Dynamics International (CDI), which is funded to derive iPSC lines from 3,000 donors using a proprietary non-integrating episomal vector system. To ensure the quality of the lines, each one undergoes a rigorous quality control (Chromosomal Integrity, Pluripotency, Identity Confirmation, Loss of Reprograming, Mycoplasma, and Sterility) prior to being banked by the Coriell Institute. A majority of donors are also screened and negative for HIV, HBV, and HCV.

The resource it is currently comprised of hundreds of iPSC lines with extensive clinical data. The specimens are presented to users via Coriell’s online CIRM hiPSC Bank catalog (catalog.coriell.org/CIRM) where users have the ability to perform detailed clinical data searches, browse dedicated disease and sample pages and place orders. Importantly, each of these iPSCs are fully licensed to ensure Freedom to Operate for commercial entities. The overall quality of these lines, Freedom to Operate, available clinical data, and accessible catalog experience makes this an unmatched resource for researchers.

The CIRM hiPSC Bank at Coriell contributes to fulfill CIRM’s mission of accelerate stem cell treatments to patients with unmet medical needs by making high quality iPSCs publicly available worldwide to investigators from academia, non-profits and industry.

Details

Start:
June 22, 2016
End:
June 25, 2016
Website:
http://www.isscr.org/home/annual-meeting/san-francisco-2016

Organizer

International Society for Stem Cell Research

Venue

Moscone West
800 Howard St.
San Francisco, CA 94103 United States