Most adult cells can only divide to produce other cells of the same type – for example, skin cells can only make other skin cells. In contrast, embryonic stem cells are ‘pluripotent’, i.e. able to give rise to all the different kinds of cell that make up the human body. However, researchers are now able to reprogram adult cells such as blood or skin cells, to create induced pluripotent stem cells (iPSCs). Like embryonic stem cells, iPSCs are able to generate any kind of cell; as such, they offer researchers a good supply of different kinds of human cell types which can be used in research and drug development.
When EBiSC began, iPSCs were still a relatively new technology. Although many human iPSC lines had been created, their quality varied enormously and few were accompanied by sufficient background data such as consent information and confirmation of cell line identity. Furthermore, access to many lines was tightly restricted, meaning demand for good quality iPSCs vastly outstripped supply.
EBiSC, a non-profit biobank, now provides the global science community with over 800 cell lines derived from patients diagnosed with neurodegenerative, cardiovascular and eye diseases, diabetes, and muscular dystrophies, as well as healthy donors. The cell lines were created and deposited in the EBiSC catalogue by iPSC centres across Europe including a number of other large iPSC research projects (such as the IMI project StemBANCC). Moreover, the project established standardised solutions for the expansion and differentiation of cells, whilst development of a robust quality control (QC) regime means that cell lines from EBiSC contribute to improving the reliability of research results. This is important when one considers that all too often, researchers are unable to replicate the results of each other’s experiments.
EBiSC has now distributed iPSC lines to users across the world, including USA, Australia, New Zealand, Japan and Korea, in addition to users across Europe. Collection and distribution of iPSC lines on this scale would likely not have been possible without establishment of an Information Management System, supporting EBiSC with gathering cell line data, managing cell line documentation and controlling availability across hundreds of lines. In addition to supplying iPSC lines, EBiSC also developed a training framework to support dissemination of best practice for the culture and banking of iPSC lines, this publically available resource supports users after receiving their iPSC lines, recommendation on routine QC to be performed in users’ laboratories to maintain high standards is also available. Underpinning these activities, the project set up a harmonised ethics and legal governance framework for the deposit and distribution of iPSC lines, and established harmonised donor consent forms which have been used across Europe, including other IMI projects such as PHAGO and ADAPTED.
These project results were only possible because of the broad collaboration between academics, the pharmaceutical industry, and SMEs. The project provided a platform for extended networking and exchanging of stem cell-related expertise across the consortium, and this allowed individual research institutions to standardise experimental procedures in alignment with the state-of-the-art quality criteria that were defined by the whole consortium.
More broadly, EBiSC has demonstrated that large scale, automated expansion and differentiation of iPSCs is feasible, making high-quality stem cells and their derivatives available for future applications at industrial scale in a cost efficient manner. EBiSC2 will take this to the next step, performing iPSC banking and differentiation across multiple lineages and supplying differentiated products directly to users. In the long term, EBiSC will undoubtedly help to promote Europe as an attractive place for biopharmaceutical research and development and provide a new and major resource for future medicines development which will improve the health of European citizens. It will also contribute to reductions in the use of animals in research, as the use of iPSCs replace tools and studies that use animals.
For the benefit of industry, academia, SMEs
Throughout the project, scientists from multiple academic centres across Europe gained access to high-quality iPSC lines, thus reducing their reliance on poor quality cells. They also gained access to genomic data sets supporting research activities; awareness of best practice in banking, cryostorage and quality control; and access to virtual training ensuring the quality of their research. Additionally, the use of the ethical framework for the collection of biological samples suitable for iPSC generation and distribution, was translated across the academic community whilst a streamlined process for iPSC line deposition ensures that newly generated lines can be stored and distributed by a central non-profit bank.
SMEs also benefited from access to the iPSC lines. In addition, working with pharmaceutical companies gives SMEs valuable insights into the needs of the larger companies. For their part, the pharmaceutical companies in the project are now using the EBiSC iPSCs in their active research to study diseases and develop new treatments, for example in the neurological disease field. They also benefited from access to the state-of-the-art technology in the research institutes and SMEs in the project
A further IMI project, EBiSC2 is now building on the work begun under EBiSC and related initiatives. EBiSC2 will extend the existing cell line collection, knowledge and infrastructure established under EBiSC ensuring the sustainability of the resource long-term.