The ISSCR Annual Meeting meeting brings together everyone in the stem cell community for scientific programming and networking opportunities that provide inspiration and insight.
The ISSCR is thrilled to be hosting the annual meeting in Los Angeles, California for the first time. Los Angeles has a booming life sciences industry that provides a compelling setting for the largest global stem cell event.
Of course, it’s also an international hub for travel and culture. Join your fellow scientists, academics, government officials, and researchers from around the world for five days of connection and collaboration – and don’t miss the sights of Los Angeles! Come see us at Booth # 421
See an FCDI Podium Presentation | ISSCR Session: Concurrent IVA: Road to the Clinic
Time & Location: Saturday, June 29 | 2:13 – 2:24pm | Concourse E, level One
Talk Title: Development of a Human Induced Puripotent Stem Cell-Derived Photoreceptor Replacement Therapy for Inherited Retinal Degenerative Diseases
Presenter: Lucas Chase, PhD, FUJIFILM Cellular Dynamics, Inc / Opsis Therapeutics
Poster Presentations by FUJIFILM Cellular Dynamics
Poster: T-2041 | Date: Thursday, June 27 | Time: 6:00 pm
Authors: David Majewski, Jing Liu, Souameng Lor, Tromondae K. Feaster (presenting author), Simon Hilcove, and Eugenia Jones
Abstract: Human cell types differentiated from induced pluripotent stem cells (hiPSC) offer an attractive human cellular platform to accelerate predictive drug toxicology and efficacy testing. Here, we present data demonstrating the utility of hiPSC-derived cardiomyocytes (hiPSC-CMs) in safety assessment and cardiac disease modeling. Clinically-defined Type I cancer therapeutics-related cardiac dysfunction (CTRCD) may be associated with cellular death, structural changes, and permanent damage while Type II CTRCD may be associated with cellular dysfunction, no structural changes, and reversible damage. In this study, we include a comprehensive assessment of CTRCD compounds doxorubicin (type I) and sunitinib (type II) across a panel of hiPSC-CMs derived from 6 apparently healthy donors (DIV 14) at three concentrations [0.1, 1.0, and 10 µM]. From these data, we were able to identify both type I and type II CTRCD by using a selected in-vitro cohort of hiPSC-CMs. These data further provide additional insight into sensitivities to cardio-oncology liabilities across different donors. Subsequently, we examined basic functional characterization data from several hiPSC-CM disease models, including hypertrophic cardiomyopathy MYH7 (R403Q), LMNA-related dilated cardiomyopathy LMNA (L35P), and Brugada syndrome type 3 CACNA1C (G490R) each with its respective isogenic control at DIV 14. We further identify the functional consequences of each mutation and demonstrate that each model recapitulates classical hallmarks of the disease phenotype. These data illustrate how hiPSC-CMs provide an excellent model system for assessing compound effects across multiple donors and disease models. Taken together, these examples help to create new avenues for safety assessment and efficacy studies, as well as serve as a template for future opportunities in cardiac disease modeling with hiPSC-CMs.
Poster: F-3172 | Date: Friday, June 28 | Time: 7:00 pm
Authors: Beatriz Freitas (presenting author), Tom Burke, Sarah Burton, Michael Hancock. Simon Hilcove, Kwi Hye Kim, and Deepika Rajesh
Abstract: Neuroinflammation and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Microglia, the resident immune cells of the brain, have also emerged as essential players in neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on microglia, the innate resident immune cell of the central nervous system. TREM2 recognizes a broad spectrum of polyanionic molecules including lipopolysaccharides of bacteria, sulfated glycosaminoglycans, and phospholipids. Upon stimulation, TREM2 on microglia associates with the adaptor protein TYROBP/DAP12 leading to a widespread immunoreceptor tyrosine‐based activation motif (ITAM)‐mediated signaling. This can result in proliferation, survival, phagocytosis, phagocytic oxidative burst with the production of reactive oxygen species, as well as pro‐and anti‐inflammatory cytokine expression. Loss‐of‐function mutations of TREM2 and TYROBP have been linked to the development of Nasu–Hakola disease, an inflammatory degenerative disease of the brain and bone, leading to premature dementia and death. Rare variants of TREM2 are associated with an increased risk of developing AD (Fig. 1). Most TREM2 mutations found in AD risk variants are heterozygous mutations that impact the binding of TREM2 ligands or the shedding of the extracellular domains. Parkinson’s disease (PD) affects ~1% of people over the age of 65 and is the second most common neurodegenerative brain disorder. Αlpha-synuclein (SCNA) is a 140 amino-acid protein, expressed highly in dopaminergic neurons of the substantia nigra
pars compacta and is intracellularly localized in presynaptic terminals. Alpha-synuclein proteins have the capacity to selfassemble, from unfolded monomers to oligomeric species, to
heavy aggregates (called amyloid fibrils). Accumulation of these insoluble fibrils progressively promotes the formation of intracellular inclusions called Lewy bodies within neurons and glial
cells. Recent studies suggest that α-synuclein oligomers bind to lipids, disrupt cellular membrane integrity, induce microglial activation leading to the death of dopaminergic neurons (Fig. 2).
The combination of cutting-edge genome-editing and induced Pluripotent stem cell (iPSC) technologies offers the opportunity to study patient-specific risk factors or disease-specific mutations, such as the SCNA (A53T) or TREM2, in a relevant cell type Microglia and compare the function and phenotype in a series of assays to cells derived from isogenic apparently healthy normal (AHN) iPSC lines. This approach is valuable for disease modeling, drug discovery and understanding the pathobiology of neurogenerative diseases.