Stem Cells


Unlocking the full potential of induced pluripotent stem cells for drug discovery


Human stem cells were once viewed primarily as regenerative materials for tissue repair through cell therapies. However, advances in technologies and protocols mean that induced pluripotent stem cells (iPSCs) are now playing an increasingly important role in disease modelling and human cell-based screening assays. This roundtable explores what this means for drug discovery.


T


he pharmaceutical industry’s current issue with attrition in the R&D pipeline is com- plex and multifaceted. However, few


would disagree that one of the biggest factors con- tributing to the poor rate of success in drug discov- ery is the lack of reliable and translationally useful disease models. No matter how carefully studies are designed,


animal models and immortalised cell lines cannot reflect the full complexity of human biology and disease mechanisms. While the use of human pri- mary cells or human tissue samples is an attractive alternative for drug screening, these materials can be difficult to obtain, and require additional ethical considerations. A more physiologically-relevant approach to the


preclinical evaluation of drug efficacy and toxicity is the use of stem cells. Stem cells have the unique capacity for indefinite self-renewal and the capabil- ity to differentiate into multiple cell types.


Drug Discovery World Fall 2018


Pluripotent stem cells (PSCs) can differentiate into most cell types of the body, while tissue-specific stem cells, such as hematopoietic stem cells (HSCs), can differentiate into all mature cell types for a given tissue. Human iPSCs possess a number of important


properties that make them an excellent source of cells for disease models and compound screening assays. Not only do they have the potential to gen- erate the full range of human cell types, they can be derived from any individual, even a patient. Consequently, patient samples can be used to create iPSC lines that harbour disease-causing mutations, which can subsequently be genetically modified to correct the mutation and study the disease in more detail, or to correct the cells for the development of novel cellular therapies. iPSCs generated from healthy donors can also be genetically modified to introduce disease-causing mutations to validate specific targets in the pathogenesis of a disease.


45


By Abby Edwards and Dr Richard Massey


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72