Here at Assay Depot, for the past few weeks we’ve been running a series of blog posts about stem cells discussing why iPS make an attractive research model. These reasons include:
- iPS cells avoid the ethical stumbling blocks that have tripped up embryonic stem cell research.
- Previously inaccessible patient cell types (cardiac cells, neurons) can be derived from iPS cells, and used to create “disease in a dish“.
- Potential drug candidates can be screened for efficacy or toxicity against populations of human cells that are the in vivo drug target, potentially reducing the cost and time involved in drug discovery.
iPS cells are becoming widely used as a research tool, not just as a subject of academic research. As people apply iPS technology to an increasing number of biologic questions, it is important to not overlook the shortcomings of iPS cells in research.
iPS cells can’t be differentiated into all cell types
Stem cells are theoretically pluripotent, but in practice it’s not yet known how to differentiate stem cells into every cell type of the body. Furthermore, where scientists have succeeded, such as in differentiating cardiac cells, they have not been able to achieve specific subtypes of cells, such as pacemaker cells. It’s possible to create “disease in a dish” by differentiating reprogrammed iPS cells from patient populations, but we are limited in the types of cells we study and diseases we model.
iPS cells model some diseases better than others
iPS cells are suited to modeling diseases that fit a certain profile. For clear-cut results, they are most appropriately applied to diseases caused by a single genetic mutation with complete penetrance. The genetic mutation should affect the differentiated cell being studied. Diseases that are caused by one cell acting on another require co-culture or 3D culture to establish proper relationships between cells. These diseases are difficult to recapitulate in vitro.
iPS cells have variability from reprogramming
Somatic cells can be reprogrammed by a number of methods, including integrating or non-integrating viral and non-viral approaches. The end result is the same: transcription factors are introduced that turn terminally differentiated cells into pluripotent cells. That said, differences between reprogramming methods can lead to downstream experimental ‘noise.’ Observed differences between experimental groups need to rise above the background variability between iPS cell lines. To confirm results, researchers should consider reproducing experiments using iPS cells derived from multiple donors and reprogrammed by a variety of methods.
IPS cells are a relatively new technology that straddles the line between being a field of research and being a research tool. Moving forward, both stem cell specialists and non-specialists will inform the field. In time, the challenges associated with using iPS cells will become more clearly defined and minimized, opening the field to even more researchers from both basic science and industry.
M. Bellin et al. Induced pluripotent stem cells: the new patient? Nature Reviews Molecular Cell Biology 13, 713-726 (November 2012) | doi:10.1038/nrm3448