Some Inconvenient Truths About iPS cells

My lab studies iPS cells. We are excited about iPS cells and they have enormous potential.

However, there are some realities about iPS cells related to safety that impede our ability to use them to treat patients any time soon. We must solve these roadblocks before we can move forward, but interestingly, these facts are only rarely discussed.

1) During iPS cell formation, many non-iPS cell colonies are created side-by-side in the same dish and many of them are composed of cancer cells. As a result, a key issue is the purity/clonality of a given iPS cell line.  It is even possible to accidentally ‘pick’ (i.e. select for expansion as a line) two colonies one on top of the other, but of different properties.

2) Many intermediately-reprogrammed cells have almost all the same properties as true iPS cells, but may be less therapeutically useful and more tumorigenic. Identifying and avoiding such ‘near misses’ may be nearly impossible. These psuedo-iPS cells may express most or all of the core pluripotency marker genes and may even be able to form teratoma-like tumors, but subtly lack the ability to differentiate normally into all 3 germ layer derivatives.

3) iPS cells change over time in culture. While the same can be said of ES cells, iPS cells are likely to be inherently less stable than ES cells since iPS cells underwent the dramatic reprogramming events.

4) iPS cells have genetic abnormalities (Chr. 12) that are shared with tumor cells as revealed by work by Nissim Benvenisty published in Cell Stem Cell.

5) We currently know very little about the tumorigenicity of iPS cells.

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