Scalability of iPSC Technology for Future Drug Discovery and Therapy Event Summary

Written by RegMedNet

In this conference report from the EBiSC meeting on Scalability of iPSC Technology for Future Drug Discovery and Therapy, Mark Tognarelli discusses some of his highlights.

The National Institute for Biological Standards and Control (NIBSC) co-organized a workshop with the EBiSC consortium to disseminate the experiences of key opinion leaders in the iPSC field. This took place over two days, in Berlin, on 2—3 November and saw over 90 registrants from across the globe attend representing a mixture of academia, industry, Government, not-for-profit and SME organizations.

The European Bank for Induced Pluripotent Stem Cells (EBiSC) was established to provide high quality induced pluripotent stem cell (iPSC) lines with a range of diseases, allowing researchers access to iPSC lines which otherwise would be very time consuming to acquire and derive. With the first lines released in 2014, EBiSC now has over 400 lines including 26 diseases and 250 controls from healthy donors.

Presentations on the first day covered topics relating to large scale bio-banking and saw EBiSC members discussing the challenges they had encountered and learning they had acquired over the course of the EBiSC project. A common theme which arose throughout the day was the need for appropriate consent, and particularly the need to demonstrate consent has been given. With the vast amount of resources and infrastructure required to build banks of readily-available human pluripotent stem cell (hPSC) lines, the lack of demonstrable consent (which in some cases has been difficult to locate) has the potential to undo any established supplier of hPSC lines. 

Further challenges came from the experiences of establishing a bank with lines generated from multiple institutions based in different countries, where varying requirements for consent made it unclear which consent was appropriate. It was acknowledged that international efforts had been made to create a universal set of guidelines for appropriate consent but there was no clear consensus on how this would be adopted globally. In establishing such consent consideration should also be given to the eventual use of an hPSC line. Often consent is favorably provided for research purposes but not for commercial applications. 

Understanding this early on is critical to avoid banking a line and later discovering the supply of the line is restricted by the original consent. 

“The challenge of achieving a unified approach to documenting consent is vast – every individual country, hospital and institution will need to maintain control over their own ethics policy, despite any global consensus” – Glyn Stacey, International Stem Cell Banking Initiative

It was also great to see Dr Florian Merkle from the University of Cambridge presenting his work on how stem cell cultures acquire p53 mutations. 

This raised the question on how much characterization is necessary for assuring that any particular stem cell line is safe for human application. Whilst it has long been known that extensive passaging of cell lines can lead to chromosomal abnormalities, the development of techniques such as whole genome sequencing allow for the detection of mutations previously too expensive to screen. It is not clear to what extent these mutations are clinically significant. Dr Merkle believed the significance of these mutations would be determined by the level of risk which was willing to be accepted.

“I don’t think the questions is would I put a therapy [made with hPSC lines know to contain mutations] into myself, this is an obvious answer, but would I be willing to put these therapies into my son?” – Dr. Florian Merkle

The second day was themed around the applications of stem cell bio-banks and began with a scientifically engaging presentation from Professor Christine Mummery. Prof. Mummery discussed the work being undertaken at Ledien University (Netherlands) where the researchers are focusing on obtaining quantitative data from iPSC-derived cardiomyocytes with the intention to develop assays for screening pharmaceutical drugs. This was followed by a talk on the work at I-Stem in France where Dr. Marc Peschanski discussed what he believed were the requirements for taking stem cell based therapies into the clinic. This addressed all aspects of potential therapies; from the creation of haplobanks, to match HLA types for significant proportions of the population, to the use of closed systems for keeping the costs of these therapies to a minimum.

The contrast between these two talks reflected the diverse applications of hPSCs and raised the question of how long it would be until a range of iPSC-based therapies would be licensed, with a wide variety of opinions aired on this topic. 

The final talk was from the Human Pluripotent Stem Cell Registry (hPSCreg) Principal Investigator Dr Andreas Kurtz who provided an overview of the hPSCreg database which provides a free resource of information on stem cell lines across the world as well as certified hPSC lines for use in EC funded research.

The hPSCreg database received strong support from delegates who recognized the importance for this type of database and praised hPSCreg’s willingness to work with all international groups. The importance of databases like hPSCreg is not only key for immediate research but for future investigators looking to access lines they have found in scientific literature, often which have multiple names. 

The EBiSC consortium would like to thank everyone who attended and contributed to the workshop. All the presentations from this event were recorded and can be expected to be made available through the EBiSC website in December. A workshop report will also be published in 2018.