Stem Cells
STEM CELL differentiation
Stem cells are extraordinary cells, capable of both self-renewal and differentiation to mature somatic cells in vivo and in vitro1,2. They have many features and advantages which could revolutionise drug development and healthcare applications.
S
tem cells offer a limitless, consistent supply of physiologically relevant cells from validated pathogen-free sources for applications such as cell replacement therapies, drug discovery, dis- ease modelling and toxicology studies. The ground-breaking emerging field of induced pluripotent stem cells (iPS cells) in which somatic cells can be reprogrammed to a pluripotent stem cell state1 has further increased interest in stem cell technology. iPS cells present the opportunity to generate patient and disease specific cells for cell therapy and disease modelling. However, a critical barrier to the use of stem cells in these therapeutic and drug development applications is the difficulty in routinely directing their differentiation to repro- ducibly and cost-effectively generate pure popula- tions of specific cell types. In this article we will describe the current state-of-the-art in stem cell dif- ferentiation and some of the latest innovative tech- nologies that are greatly accelerating improve- ments thus driving the adoption of stem cells in biopharmaceutical applications.
Stem cell applications
Stem cells have been utilised in cell replacement therapies for more than 40 years in the form of bone marrow transplantation3. Haematopoietic stem cells (HSCs) are present in bone marrow at a very low frequency but are capable of reconstitut- ing the entire blood system of recipient patients4. More recently, other stem cell treatments have
Drug Discovery World Winter 2011/12
progressed to the clinic, for example ReNeuron’s neural stem cells for treatment of Stroke5 and Mesoblast’s adult stem cell Revascor™ therapy for congestive heart failure. However, the high cost of manufacture of these treatments along with a complicated and poorly understood regulatory pathway is hampering the widespread develop- ment of stem cell therapies.
An alternative application of stem cells is their use in the discovery of conventional small molecule drugs for which the regulatory and manufacturing pathways are well established. Stem cells have application in all stages of the drug discovery path- way from target identification through to toxicolo- gy studies. Since they can be propagated for pro- longed periods of time, cryopreserved and differen- tiated to physiologically relevant cell types they have significant advantages over currently used models such as recombinant cell lines and primary cells. Furthermore, iPS cells now offer the oppor- tunity to generate disease-specific somatic cells6 and to rapidly generate panels of stem cells with a range of genetic phenotypes, allowing genetic effects on drug performance to be studied. Differentiation to functional hepatocytes and car- diomyocytes also opens the opportunity for the use of stem cells further down the drug development pathway, in critical toxicology studies. There are few reports of true high throughput screening (HTS) campaigns using stem cells, however Pfizer has carried out one such screen providing proof of
71 By Dr Lilian Hook
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