EPAA STEM CELLS PROJECT

Transcription

1 EPAA STEM CELLS PROJECT Belén Tornesi AbbVie - EPAA Platform on Science - Stem Cells Forum Platform on Science 1

2 Platform on Science Shifting from the traditional paradigm Not looking for an 1:1 replacement of the current animal tests but for new ways of doing science and safety assessment Shifting from the more traditional work of Replacing, Reducing or Refining to: a more science-based ambitious approach less method-specific approach Allowing better cooperation for multidisciplinary research : between sectors between regions Current initiatives: USA: Toxicity Testing in the 21st Century (US National Academy of Sciences), FDA s Regulatory Science EU: EPAA s New Perspectives on Safety/Computational chemistry/stem cells, SEURAT-1, AXLR8, New challenges for Risk Assessment (EU Scientific Committees) Platform on Science 2

3 PoS Starting Point: Workshop on New Perspectives on Safety, Brussels, April 2008 Eminent scientists from different disciplines under the moderation of the Editor-in- Chief of Nature: Dr Philip Campbell Workshop Objective: To define and advise the research needed to enable future hazard identification on chronic repeat dose systemic toxicity to reduce the use of animal testing. Platform on Science 3

4 Workshop Recommendations (2008) Establish task forces to examine how to exploit recent scientific and technological developments: a) In Stem Cells Research b) in Computational Chemistry plus Systems Biology Platform on Science 4

5 EPAA Stem Cell events - overview October 2009, Ispra, Italy Workshop Stem Cells in safety testing a new strategy Discussion on how the (intensive) research using SCs would fit in less use of animals for safety testing October 2011, Ispra, Italy Workshop Stem cells and their derivatives in toxicological research programs and as a possible regulatory tool: A gap analysis Identification of opportunities to develop and gaps to fill by ongoing and future SCsl programmes Exploring the possibility to establish a permanent forum Result: Formation of two working groups, both consisting of EPAA members and academic experts Working group 1: Communication on stem cells Working group 2: Fundamental research on stem cells April 2013, London kick-off meeting Stem Cell Forum with the vision of establishing a permanent forum August 2013, Brussels Workshop Stem cell derived organ like models for analyzing mid and long term dosing dynamics studies Platform on Science 5

6 Identified Needs and Workshop Recommendations (2011) #1: A contemplated step towards better harmonisation of research initiatives: constitution of an international forum #2: Expansion and detailing of knowledge of SC basic biology for efficient and reliable SC-based predictive tox. testing. In particular: stem cell derived organotypic cultures (3D); Relevance of stem cells for carcinogenicity assays; differentiation between adaptive response and adverse perturbation; translational aspects of stem cell use #3: Efficient communication network regarding reference compounds, as a central tool to gather and share information about specific organ toxicities. Platform on Science 6

7 Follow-up of Workshop Recommendations (2011) Establishment of an Expert Working Group Communication (1. subgroup of the Stem Cell Core team) Kick-off meeting to assess the options for establishment of an International Stem Cell Forum, April 2013, London Establishment of an Expert Working Group on Fundamental Research (2. subgroup of the Stem Cell Core team) Scientific workshop on Stem cell-derived organ-like models for analyzing mid and long-term dosing dynamics, August 2013, Brussels Platform on Science 7

8 International Stem Cell Forum London, April 2013 Objectives of the SC Forum To establish a permanent non-commercial International Stem Cell Forum to explore the types of stem cells used in toxicology and their applications. To provide a platform, EPAA acting as a facilitator to build trust and relationships encourage open dialogue between existing consortia/researchers identify and share common problems and potential solutions appropriate for the wider community To facilitate collaborations between groups active in stem cell research for toxicity assessment To accelerate translational applications and acceptance by regulatory agencies Platform on Science 8

9 International Stem Cell Forum April SC Key issues identified Standardisation of assay protocols Choice of reference compounds Importance of maturity of cell phenotypes Definition of criteria for validation and acceptance of new models Epigenetics Platform on Science 9

10 Permanent Stem Cell Testing Forum Steps for implementation Web-based tool for Compound sharing Priority lists Synergy identification Workshop by mid 2014 Benchmarking of stem cell assays in safety assessment across international consortia In depth discussions of identified relevant topics with an emphasis on decisions being made and published as a perspective white paper in an impactful journal Platform on Science 10

11 Workshop on Stem Cell Fundamental Research August 2013, Brussels Stem cell-derived (SCD) organ-like models for analysing mid and long-term dosing dynamics Scope & Goal of the Workshop Support use of stem cell-derived target cells for compound testing in industry by discussion of four main topics Formulation of a Research Prospectus as a recommendation to the European Commission, stakeholders in industry and funding bodies, to launch a research call and fund research program(s) Publication of outcome of the discussion as flash report and white paper Documents currently in preparation Platform on Science 11

12 Scientific Focus of the SC Fundamental Research WS Represented scientific expertise (26 invited experts) Cutting edge stem cell research (& SCD target cells) Toxicology Metabolism and Kinetics Advanced technologies for complex cell cultures EPAA representatives from: Pharma, Chemicals & Consumer Care Areas of Focus TOPIC 1: Stem-cell derived test systems for the evaluation of dynamic processes in the whole organism TOPIC 2: Identification of methods to generate organ-like cell or tissue models originated from stem cells (e.g. 3D models) for compound testing TOPIC 3: Toxicologically relevant endpoints and Adverse Outcome Pathways TOPIC 4: Requirements for a stem-cell based system to gain scientific and regulatory acceptance Platform on Science 12

13 Identified areas of focus for future research in Europe* Relevance, characterization and validation of SC-derived systems Physiologically and toxicologically relevant Fit for purpose Well characterized, robust and reproducible Inclusion of ADME-parameters in (SC-derived) cell-based assays Use of physicochemical properties and PKPB-modelling (multidisciplinary approach) Establishment of sensitive and fast (high throughput) methods for the determination of cellular exposure to compound and metabolites Identification of toxicologically relevant cellular pathways Study of molecular endpoints to distinguish adaptive from adverse responses Assess cell-type specificity by using both differentiated and undifferentiated SC-derived cells Study interplay of different cell types by organoid-like mutlicellular 3Dsystems *Funding by the EU or other governmental bodies on these areas of research should be encouraged. Discussion between EPAA and funding bodies planned Platform on Science 13

14 Conclusions Communication group: Working to establish the permanent platform: Collaborations, translational applications and 5 keys issues identified Fundamental Research group: Identified 3 areas of research that should be funded Discussion with funding bodies and publication of the outcome planned Regulatory acceptance?... Platform on Science 14

15 Thank you! ISPRA WS 2011: Stem cells and their derivatives in toxicological research programs and as a possible regulatory tool: A gap analysis Klaus-Dieter Bremm, Bayer Brett Cochrane, Unilever Belén Tornesi, Abbott Mario Beilmann, Boehringer Ingelheim Julie C. Holder, GSK Martina Klaric, ECVAM Susanne Bremer, ECVAM Gaby Küsters, EPAA project support Platform on Science 15

16 Thank you! London Forum kick off: Stem cell permanent forum? Frank Bonner, SC4SM Anthony Holmes, NC3Rs Laura Suter-Dick, University of NW Switzerland (FHNW) Belén Tornesi, AbbVie Beatriz Silva-Lima, Lab.Pharmacology Lisboa Gaby Küsters, EPAA project support Fundamental Research WS Brussels Mario Beilmann, Boehringer Ingelheim Klaus-Dieter Bremm, Bayer Laura Suter-Dick, consultant Magnus Ingelman-Sundberg, Karolinska Institute Pratibha Mistry, Syngenta Paul Fowler, Unilever Jürgen Hescheler, University of Cologne Adrian Roth, Roche Donald B. Stedman, Pfizer Gaby Küsters, EPAA project support Platform on Science 16

17 Platform on Science 17