Major Applications of iPSC

Consistent supply of standardized, high quality iPSC lines from the EBiSC facility is envisioned to greatly facilitate many categories of research in this important area of stem cell science. These span from the intricacies of the mechanism of reprogramming to factors determining pluripotency and how individual cell fates are programmed in stem cells. Biotech companies and SME research into the development of new cell processing procedures which are more reliable, affordable and efficient, will also be assisted via access to EBiSC’ iPSC lines.

The areas that are most likely to benefit however relate to industry based research to understand the genetic basis of disease, how individual patients within a given diagnosis are different, the development of new medicines as future treatments and in support of clinical research to understand individual patient responses to medicines being tested.

Typically medicines fail during clinical development due to lack of efficacy, even when they have been demonstrated a 'priori' to be safe. This is most likely due to a lack of use of disease relevant human cells early in pre-clinical phases of development. The EBiSC project will provide a human iPSC repository to address this and thereby make future drug development more effective. 

The disease representative cell lines will be differentiated into relevant tissue types and used in phenotypic screens by EBiSC’ pharmaceutical company partners to identify compounds that cause a desirable change in phenotype. Typically the biological target of the compound is not known at this stage and the screen is designed to model disease in the cell culture dish, so that a detectable phenotypic change correlates with prospects of symptom or disease modification. 

Cells differentiated from the iPSC lines also express disease associated changes in biochemical pathways in the appropriate physiological setting and thereby can be used in assays by the project’s pharmaceutical company partners to validate targets that have been previously hypothesized as potentially disease modifying. Validation in a cellular context is considered better than studying the action of the compound on the purified target in isolation.

Results from either type of screen can contribute greatly to the pre-clinical determination of the mechanism of action of a future drug, with statistical analysis now showing that a clearer understanding of this important aspect early leads to a higher probability of drugs succeeding later in clinical development.

By far the most exciting prospect to emerge from the industrial use of disease relevant iPSC lines, is a realization that the technology can assist drug developers by identifying individual patient's disease at the molecular level and then to utilize targeted treatments (possibly in combination) to address that individual patient's disease process. This precision medicine approach is based on the ability to better stratify into different treatment groups, those individual patients who originally have been given a single type of diagnosis and relies on correlating a patient’s genotype with their cellular phenotype and pinpointing inter-personal differences of diverse molecular pathology. In such a way developers are able to design more efficient, affordable clinical studies targetted to the precise category of patients in a shorter period of time.

Even once a medicine is approved and being prescribed to many patients across the world, iPSC technology may play an important role in future pharmacovigilence by providing a cell based assay to identify the molecular correlation of individual patient drug response variations. 

Automated cell culture © Fraunhofer IBMT, Photo: Bernd Müller