Periodic Reporting for period 3 - EBiSC2 (EBiSC2 – A sustainable European Bank for induced pluripotent Stem Cells) Période du rapport: 2021-09-01 au 2023-02-28 Résumé du contexte et des objectifs généraux du projet EBiSC2 has established a self-sustainable European-based and globally operating repository for human induced pluripotent stem cells (iPSCs). EBiSC2 seamlessly builds on the achievements of the initial European Bank for induced Pluripotent Stem Cells project (EBiSC1, funded 2014-2017) in centralising existing capacities across Europe for banking and distribution of iPSC lines and provision of related services. EBiSC2 has deployed a business strategy for a sustainable bank providing access to disease-relevant, qualified iPSCs, along with comprehensive data for research use by academic and commercial organisations. To meet evolving requirements from academia and industry, EBiSC2 is distributing iPSCs and derived cells and has extended its offering with iPSC services, while reducing operational costs through state-of-the-art upscaling, bulk production, and automation. Proof-of-concept studies (PoC) performed by academia and industry have demonstrated the reliability and robustness of the lines for disease modelling and screening and have enriched the EBiSC2 catalogue with novel data. EBiSC2 focused on collaboration with other iPSC programs and allowed the repository to serve as a central hub for EU-funded projects to bank their iPSC lines and collect associated data, thus enabling long-term access to outputs of European investments, by the research community. Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent ESTABLISHMENT OF SELF-SUSTAINABILITYA final EBiSC entity and business plan for longevity and sustainability of EBiSC has been approved by the EBiSC2 consortium and implementation is in progress. This includes:o Availability and delivery of EBiSC2’s new iPSC products, such as gene edited (GE) disease lines, isogenic control lines and iPSC-derived cells like early neurons to meet long-term economic and scientific sustainability goals. o EBiSC iPSC services (e.g. reprogramming, GE, banking, quality control (QC)), highlighted via the catalogue, with quotes to academic and industrial Users already provided.o A refined and extended IT infrastructure to better meet current and future requirements of the EBiSC bank and its customers while reducing future maintenance efforts.o An updated ethical, legal and data management framework for safeguarding and sharing of iPSCs and data.o Continued and proactive contact with researchers and funders across Europe. o Engagement with scientific community via existing and new approaches such as new EBiSC informational videos and participation in scientific meetings.o Synergistic collaboration between EBiSC and hPSCreg to jointly provide key infrastructure for iPSC cells and data.o Ongoing monitoring of prices for cell lines and services to achieve a sustainable Bank and allow investment into new technologies and cell lines.EXTENDING EXISTING CELL LINE COLLECTION AND PRODUCT PORTFOLIO- iPSC-neurons from a healthy cell background with capability for rapid maturation and functionality are released on the catalogue as EBiSC2’s first iPSC-derived cell offering (EBiSC-NEUR1), and next upcoming derived cells from other lineages have been identified and are in development.- New EBiSC2 iPSC lines have been deposited and are available via the catalogue including novel tool and disease lines.- EBiSC2 has enriched existing iPSC lines via the addition of new data (e.g. clinical data) and by increasing searchability and accessibility of existing data (e.g. annotating lines with genetic variants pulled from genomic data).- EBiSC2 has made connections with new clinical teams via disease research groups and has assessed collection of donated biosamples for its on-demand iPSC service portfolio.- Via dissemination activities, EBiSC2 has highlighted support of third-party research projects by accelerating and safeguarding outputs such as iPSCs and data including scientific publications and presentations at scientific meetings and pitching at funder-led networking sessions have been designed to communicate these aspects and engage new depositors and research partners. - EBiSC2 has continued funder engagement to support integration of new iPSCs into EBiSC, ensuring that ethical and legal provenance and iPSC best practice is ingrained in projects from the outset. EXTENDING EXISTING INFRASTRUCTURE- Distribution infrastructure for iPSC-derived cells was established and implemented including cryostorage and shipment of alternative formats (e.g. iPSC-differentiated cells pre-plated on multi-well plates and iPSCs cryopreserved at high density in cryobags) towards high throughput applications. - Operational infrastructure for worldwide distribution was extended with new distributors for key geographical territories. New partnerships with third-party companies were explored to further increase exposure to the EBiSC product portfolio.- The EBiSC catalogue was further extended with new filter options to improve User experience and the EBiSC IMS was developed to enable management of derived cell products. - Fully updated and GDPR compliant ethical and legal frameworks, data management plan, user guidance documents and product identifiers have been established, supporting the generation and distribution of EBiSC derived cell products. EXTENDING EXISTING KNOWLEDGE STRENGTHENING SCIENTIFIC EXCELLENCE- Several PoC studies on i) maturation, functionality, and relevant pathophysiology in central nervous system disease models; ii) functional characterization and drug screening with hepatocyte model; and iii) differentiation, functional evaluation, and relevant compound testing of healthy and disease associated cardiomyocytes, were completed as collaborative cross-partner studies. - Novel iPSC lines were generated and deposited to accelerate iPSC differentiation and disease modelling including the development of innovative co-culture models. - Protocols for scalable expansion, differentiation and cryopreservation including alternative cryopreservation formats have been further optimised for iPSCs as well as neuronal, cardiac, and hepatic cell models to support reproducible and reliable PoC studies via delivery of centrally produced cell batches.- QC testing regimes for iNGN2 neurons as well as cardiac, definitive endoderm, hepatocyte progenitor and hepatocyte-like cell populations have been developed with inputs from academic and industry perspectives, including functional characterisation of a cardiac disease model. Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent) EBiSC2 has supported third-party research projects in reaching sustainability goals by providing best practice guidance and working with them to incorporate, safeguard and distribute newly generated iPSC lines into the repository. Pre-differentiated iPSC-neurons are now available as a standard product via the EBiSC catalogue with User protocols and linked publications included to support researchers in their implementation. Additional derived cell products representing other cell types are in development and upcoming during 2023.Through these activities, the global community of stem cell scientists and researchers can access not only the iPSC lines but also access to relevant and steadily growing datasets, supported by the stable integration with hPSCreg within the core banking framework. This enables EBiSC to, at high volume, assign unique identifiers, collect cell line data, and allow users to search for specific information for iPSCs. Based on current and future forecast sales, EBiSC will achieve its ambitious goal of self-sustainability. EBiSC2 project logo
