Tuesday, March 25, 2014

You Can Bank on Stem Cells!

Stem cell research has remained in the spotlight for the better part of a decade now, for better or for worse. Since the discovery of human embryonic stem cells (hESCs) questions pertaining to their moral and ethical procurement and use for research and treatment has been scrutinized. Many of these issues were quelled by the discovery that somatic cells could be reprogrammed to a state similar to that of the hESC (i.e. pluripotent)  Most recently, Nature reported work surrounding a new methodology for reprogramming human somatic cells to a pluripotent state by chemically stressing them (likely many of us have a substantial reserve of them!) While intriguing, the report has come under scrutiny and independent verification of its usefulness as a method to generate induced pluripotent stem cells (iPSCs) remains to be seen. Regardless, the landscape is changing as reports on the use and interest in generating iPSCs with high genetic variability continues to infiltrate a broad range of scientific fields.

Early innovators in the field of stem cell biology pointed to the powerful experimental models that could be generated if easily harvested cells from an individual exhibiting a disease of interest could be reprogrammed to iPSCs.  By then differentiating these cells to a cell type particular to the disease being investigated it would be possible to examine a model with a more relevant genetic background. The use of iPSC derived cell lines would help overcome several disadvantages inherent with current models. These include primary human tissue or cadaveric tissue which have low availability and are subject to variability for a variety of reasons and immortalized cell lines that can exhibit significant alterations in biological function.  In fact many of the immortalized cell lines, such as CHO and HEK cell lines, were at the center of high-throughput screening and lead optimization campaigns over the recent past that have seen high candidate failure rates during clinical trials. It is thought that the use of cell lines with a more relevant genetic background coupled with phenotypic screening may prove more fruitful.

The increased efficiency of producing patient-specific iPSC lines over the past decade has lead to a relatively large number of cell lines derived from donors with a wide range of disease types.  As a mechanism to help provide worldwide access to the ever increasing number of available cell lines, efforts have been made to establish large banks to provide not only disease specific cells but genetically diverse iPSCs for population genetic studies. Several programs have now been sponsored in the US, UK, and China (http://www.nature.com/nbt/journal/v31/n10/fig_tab/nbt.2710_T2.html).

While the importance of such banks may be obvious the challenges are many. Significant work still needs to be done to standardize methods, characterize each cell line, improve reprogramming methods (particularly efficiency) and decrease costs. In fact cost may be the single biggest obstacle to the adoption of iPSC derived cell models by the pharmaceutical industry as the cost is estimated to be at least an order of magnitude more expensive than the use of immortalized cell lines. Without the backing of Pharma these banks may remain limited in scope if having to rely on public funds to finance future growth.

References

Novak, T.,  Grieshammer, U.,  Yaffe, M., and S. Madore (2012/14): Resetting the course of drug development: stem cell banking in support of drug discovery. In Drug Discovery World 15 (1), pp. 14–21.


By: BioTek Instruments, Peter J. Brescia, Jr., MSc, MBA, Applications Scientist


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