- 인공 유도 다능성줄기세포(iPS 세포) -

인공 유도 다능성줄기세포(iPS 세포)를 테마로 한 이 컨퍼런스 프로그램에서는 질병 모델링, 표적 발견, 리드 화합물의 최적화, 기능적 스크리닝, 약물 안전성 스크리닝 등 iPS 세포의 다양한 응용 분야에 관한 세션이 진행됩니다.

Final Agenda

Recommended All Access Package:

11월 27일: 장기 칩과 미소 생리 시스템

11월 27일 Dinner Course: 쇼트코스 3:장기 칩 시스템의 기점, 최적화, 응용

11월 28-29일: 리드 화합물의 최적화와 약물 독성 예측

11월 29-30일: 3차원 세포 모델

11월 29일 Dinner Course: 쇼트코스 5:인간화 마우스 모델:기술 개요와 암 면역치료의 전임상 평가에 대한 응용

11월 29일(목)

8:00 Registration and Morning Coffee

약물 안전성 평가에 대한 줄기세포의 이용

8:25 Chairperson’s Remarks

Christopher Goldring, PhD, Senior Lecturer, Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool

8:30 Importance of Phenotyping Your Model to Know What Purpose It Is Fit For

Christopher Goldring, PhD, Senior Lecturer, Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool

It is estimated that 38% and 51% of compounds showing liver injury in man do not show similar effects in animals. The work of the IMI MIP-DILI and TransQST consortia shows how a roadmap is being developed based for the integration of established and emerging test systems and illustrates the increasing complexity of models from 2D to multi-cell 3D systems that are used in a logical fashion to assess DILI liabilities of new drugs before they are given to man.

9:00 Bioengineering Human Pluripotent Stem Cell Derived 3D Models for Drug Toxicity and Disease Modeling

Paula M. Alves, PhD, Unit Director, Cell Bioprocesses Laboratory, Instituto de Biologia Experimental e Tecnologica (iBET)

The development and validation of human in vitro models with physiological relevance, robustness, reproducibility and scalability are still a need in toxicology. Our strategy combines human stem cells, 3D culture strategies and computer-controlled bioreactors in perfusion operation modes. Results concerning the establishment and refinement of culture systems for efficient stem cell differentiation and maturation into cardiac, neural and hepatic cells, as well as their applicability for long-term toxicity testing will be presented and discussed.

9:30 Sponsored Presentation (Opportunity Available)

10:00 Coffee Break in the Exhibit Hall

10:45 Exploring the Relationship between Myofilament Calcium and Force Production in the Single iPS-Cardiomyocytes

Matthew J. Daniels, MA, PhD, MRCP, Wellcome Trust Intermediate Clinical Fellow, Principal Investigator, Division of Cardiovascular Medicine, and BHF Oxbridge Centre of Regenerative Medicine, Oxford University

The in vitro survival of iPS-CMs should aid cardiotoxicity studies of contractility. As contraction depends on depolarisation, both parameters should be measured in these assays. We find that all classes of chemical dye (voltage, calcium & sodium) impair contractility, and when used in combination with drugs known to act on the myofilament produce confusing composite results making them unreliable for this purpose. We describe how we have overcome this problem.

11:15 Phenotypic Analysis for Cardiotoxicity Evaluation on hiPSC

Anthony Perrier, PhD, Study Director, In vitro Toxicology, Biologie Servier

To improve the early prediction of cardiac toxicity, we developed in vitro tests using High Content Analysis using human iPSC cardiomyocytes. The readouts were qualified using Receiver Operating Characteristic curves and a ranking algorithm was developed to obtain an overall multiparametric cardiotoxicity evaluation for each compound. This cardiotoxicity phenotypic analysis and ensuing improvements will be used for early safety evaluation in the drug development process at Servier.

11:45 Evaluating Cardiovascular Liability and Genetic Disease with hiPSC-Cardiomyocytes

Chris Denning, PhD, Professor and Head, Department of Stem Cell Biology, University of Nottingham

We will review the results from a public-private partnership (NC3Rs-GSK), termed the “CRACK-IT InPulse Challenge” and the software developed to facilitate analysis of cardiac contractility. This sought to evaluate hiPSC-cardiomyocytes in 2D and 3D formats in the blinded evaluation of 28 drugs that were associated with positive or negative inotropy in heart tissue, or no effect. Finally, we will show data on the coupling of hiPSC-CMs and Cas9/CRISPR-mediated gene editing to model hypertrophic cardiomyopathy.

12:15 Brief Session Break

12:20 Bridging Luncheon Presentation (Opportunity Available) or Enjoy Lunch on Your Own

12:50 Session Break

iPS 세포 기반 3차원 모델 - I

13:25 Welcome Remarks

Joel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening Remarks

Hansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

13:35 Human Heart-in-a-Jar from iPSC for Disease Modelling and Drug Screening

Ronald A. Li, PhD, Director and Professor, Ming Wai Lau Center for Reparative Medicine, Karolinska Institutet

Traditional drug development is an inefficient and expensive process with unacceptably high failure rates. Major species-specific differences limit the ability of animal models to predict human cardiotoxicity, the dominant reason for attrition. Here, I will present various human ESC/iPSC-derived engineered heart constructs that our group has designed specifically for studying electrophysiology and contractility, including our latest fluid-ejecting “human heart-in-a-jar” that uniquely enables the measurements of clinically complex parameters such as cardiac output, ejection fraction, PV loops.

14:05 An in vitro 3D Kidney Model – Generation and Application in a Pharmaceutical Setting

Anna Jonebring, MSc, Senior Scientist, Translational Genomics, Discovery Sciences IMED Biotech Unit, AstraZeneca

A disease like chronic kidney disease (CKD), affecting approximately 10% of the population, is one of the areas where there is a great unmet need for innovative pharmacological therapies. Within AstraZeneca we are working with human iPSCs derived 3D kidney models in a platform approach to drive the TI/TV activities as well as developing a highly efficient model for safety/toxicology applications. Combining the 3D model with CRISPR/Cas9, Next-Generation Sequencing (NGS), functional testing and advanced imaging techniques, our 3D kidney platform is evolving and becoming an essential part in our drug discovery process.

14:35 Sponsored Presentation (Opportunity Available)

15:05 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing

줄기세포와 iPS 세포를 기반으로 한 중추신경계 모델

16:45 Testing Drugs That Modulate Mitochondrial Biogenesis and Function in iPSC Models of Neurodegenerative Diseases

Michela Deleidi, PhD, Helmholtz Young Investigator Group Leader, DZNE

While mitochondrial dysfunction is emerging as key in neurodegenerative diseases, a central question remains whether mitochondria are actual disease drivers and boosting mitochondrial biogenesis and function ameliorates pathology. We outline how patient-derived induced pluripotent stem cells and genome editing can be used for modelling mitochondrial demise occurring in neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease. We outline progress in screening for compounds that improve energy metabolism and ameliorate neurodegenerative phenotypes.

17:15 Exploiting Human Stem Cells to Recapitulate Pathological Signatures of Human Brain Microenvironment

Catarina Brito, PhD, Lab Head, Advanced Cell Models Lab – Animal Cell Technology Unit, iBET & ITQB-NOVA

We have been exploiting platforms based on spheroid culture in perfusion stirred tank bioreactors for generation of functional neurospheroids - 3D structures containing neurons, astrocytes and oligodendrocytes, derived from human induced pluripotent stem cells. Recent data on the characterization of the cell microenvironment generated within neurospheroids will be presented. The application of neurospheroids as in vitro models to address molecular defects associated with neurological disorders that affect neural microenvironment homeostasis and as potency assays for drug testing will also be discussed.

17:45 Disease Modeling of ALS with Patient-Specific iPSC-Derived Motor Neuron Cultures

Shila Mekhoubad, Scientist II, Stem Cell Biology, Biogen

18:15 Close of Day and Dinner Short Course Registration


19:0021:30 Recommended Dinner Short Course*

쇼트코스 5:인간화 마우스 모델:기술 개요와 암 면역치료의 전임상 평가에 대한 응용

* Separate registration required.

11월 30일(금)

8:00 Registration and Morning Coffee

iPS 세포 기반 3차원 모델 - II

8:25 Chairperson’s Remarks

Marine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SA

8:30 Organoids: A Next-Generation in vitro Model That Captures Clinical Response

Lyle Armstrong, PhD, Professor of Cellular Reprogramming & CSO, Newcells Biotech Ltd., Institute of Genetic Medicine, Newcastle University

Toxicity testing based upon animal models or transformed cell lines is not always an accurate representation of the response of human tissues and organs to xenobiotic substances. The development of human pluripotent stem cells, which are capable of generating many of the cell types found in the adult body may be an effective solution to address this problem therefore this lecture will attempt to present not only the background of what pluripotent stem cells are and how they are made but also how we can use them to produce versatile new toxicity assays for use in pharmaceutical development.

9:00 In vitro Generation of Functionally Mature Beta-Cells from Adult Human iPSCs

Marine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SA

Islet transplantation has demonstrated that replacement of the beta-cell mass in diabetic patients is able to restore endogenous glycaemic control. Stem-cell therapies hold great promise for generating a replenishable supply of insulin producing beta-cells for transplantation. In the present studies, we report the in vitro generation of functionally mature beta-cells from human iPSCs. These newly generated beta-cells display mature features and exhibit glucose regulated insulin secretion, displaying the first and second insulin release phases characteristic of human islets.

9:30 Sponsored Presentation (Opportunity Available)

10:00 Coffee Break in the Exhibit Hall. Last chance for poster viewing.

줄기세포 기반 3차원 모델

10:45 Novel 3D Hepatic in vitro Systems for Studies of Chronic Drug Toxicity and Liver Disease

Magnus Ingelman-Sundberg, PhD, BSc.Med, Professor, Department of Physiology and Pharmacology, Karolinska Institutet

Using a model of 3D PHH spheroids we observed that drug metabolism was preserved for several weeks of cultivation and that transcriptomic, proteomic and metabolomics analyses revealed similar phenotype as in freshly isolated hepatocytes. In addition, using these 3D spheroid systems we have been able to mimic different liver disease like NAFLD, NASH and fibrosis and found the system suitable for evaluation of mechanisms behind and for identification of drug candidates. In the lecture recent results describing the properties and usefulness of the system will be presented.

11:15 Modeling Kidney Development and Disease through 3D Organoids

Nuria Montserrat, PhD, Group Leader, Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC)

Our aim is to facilitate basic knowledge on kidney engineering providing novel approaches facilitating renal maturation and function. We have generated kidney organoids from human pluripotent stem cells. In parallel, we have developed biomimetic inks for bioprinting 3D kidney structures. Lastly, using a novel transplantation method we have further maturated and vascularized kidney organoids. We provide innovative solutions when translating these technologies into the clinical setting.

11:45 Organoids: A Next-Generation in vitro Model That Captures Clinical Response

Robert Vries, PhD, Managing Director, Stichting Hubrecht Organoid Technologies

The laboratory of Hans Clevers, the founder of HUB, previously discovered the identity of adult stem cells in many human tissues such as intestine and liver (Barker et al., Nature 2007; Huch et al., Nature 2013). More recently, we were able to demonstrate that the in vitro response of organoids directly correlates with the clinical outcome of the patient from which the organoid was derived (Dekkers et al., Sci Trans Med 2016; Sachs et al., Cell 2018). In addition, we have now developed a novel system that allows the co-culture of organoids with immune cells to study the effect of immune modulating drugs.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Close of Conference

* 주최측 사정에 따라 사전 예고없이 프로그램이 변경될 수 있습니다.

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