Stem Cells
Stem cell technology – delivering the promise
The promise of stem cell technology as a tool for drug discovery, drug development and as a therapeutic modality is no longer in the future but part of contemporary healthcare. The speed which stem cells have been integrated into biomedical product development has surprised many, but stem cells in the form of bone marrow transplants have been around for several decades in medical practice.
M
ost drug discovery programmes now use functional, cell-based assays for target hit identification and lead opti- misation because of the desire to utilise the scien- tific understanding of signalling pathways. This has resulted in a capability to probe more complex targets and seek target modulation, rather than complete inhibition. Pharmaceutical companies have also employed stem cell technology for drug discovery and testing for more than 10 years. Stem cells may help us understand the complexity of human disease by studying cells as they become more differentiated, making nerves, skin, cartilage, bone and brain. Drug developers hope that charac- terising the signals and mechanisms of cell differ- entiation may yield information about how dis- eases arise and suggest new strategies for therapy. New medications are now tested for safety on spe- cialised cells generated in large numbers from stem cell lines – reducing the need for animal testing – and cancer stem cell lines are used to screen poten- tial anti-tumour drugs.
Thus, there are considerable efforts in adopting stem cell assays for drug discovery, since stem cells can differentiate into specific cell types that may not be available from human sources. Also, many available human cells have not been very good at predicting side-effects of newly discovered drugs as they enter the pipeline. In each example, however, it still must be proven that differentiated cells
Drug Discovery World Fall 2011
(derived from stem cells) are equivalent to the desired or target cells and can be validated as a drug screening tool. Critical areas of drug screen- ing include cardiotoxicity, mutagenicity and immunogenicity.
Cell-based assays formats play a role in testing compounds for effects on proliferation and screen- ing for inhibitors or modulators of cell growth. In addition, the effects of modulators of stem cell self- renewal will help define stem cells and their poten- tial cell fates during differentiation. Studies to characterise both the natural and desired function- ing of stem cells, progenitor cells and differentiat- ed cells will be crucial. This focus on stem cell biol- ogy has yielded innovative technologies and cell- based tools for leading-edge research. This will hopefully translate into comprehensive drug dis- covery and development programmes which can bring new medicines to market faster and more cost-effectively. Furthermore, these advances should also translate into more robust manufactur- ing processes that supply novel therapeutics to clin- ical development programmes.
High throughput discovery and toxicology plat- forms used by pharmaceutical companies require large quantities of differentiated cells – cells that mimic the spectrum of human pathologies – and, the demand for those cell banks has opened new busi- ness opportunities for companies that provide bio- logic tools and contract manufacturing services. Cell
9 By Dr Aaron Heifetz
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