Primary challenges facing iPS cells in late 2012

One of the questions I get asked most often is whether induced pluripotent stem cells (iPS cells) are well on their way to replacing ES (embryonic stem) cells.

My answer?

No. Not yet.

iPS cells are great, but the original notion pushed by some that iPS cells would somehow replace ES cells, which would be naturally phased out due to the awesomeness of iPS cells, has not become reality after 6 years.

What are the key issues and roadblocks for iPS cells?

1. iPS cell similarity to cancer cells. As we recently published, iPS cells and in fact ES cells too have substantially similarities to cancer cells. This relationship raises safety concerns that lead to the second point….
2. iPS cell regulatory issues. The FDA and international regulatory bodies such as the EMA in Europe will be careful in regulation. My lab recently published a review in Cell Stem Cell on regulatory challenges facing iPS cells translation to the clinic. These may be more substantial than those facing hESC if iPS cells are made using genetic methods.
3. iPS cell memory. Yeah, sure, if you culture iPS cells long enough their memories of the cell they used to be in their former life (e.g. a fibroblast) stored in their epigenomes may fade somewhat, but not entirely. The work of Daley and many others indicates iPS cells do indeed have memories of their existence as very different kinds of cells and those could have clinical relevance.
4. iPS cell mutations. During the cellular reprogramming process, while the epigenome is undergoing a metamorphosis of sorts, the genome is vulnerable to injury. Countless papers have documented a varying degree of mutations in iPS cells, some traceable to pre-existing mutations in the parental cells, but others that are unique to the iPS cells. Probably not by chance, these mutations tend to ontologically cluster in the cancer-related area. The functional relevance of iPS cell mutations remains largely unknown.
5. iPS cell epigenomic warts. Here I am not talking about the memory issue mentioned earlier, but rather incomplete or aberrant reprogramming events manifesting at the epigenomic level. Again, many groups have documented sometimes very large regions of the epigenome that are “incorrect” (meaning non-hESC-like) in iPS cells ranging from DNA methylation (present in the wrong place or absent) to unusual patterns of histone modifications.
6. iPS cell cost. To produce iPS cells for patient-specific therapies will be exorbitantly expensive for the vast majority of people. I would estimate that to produce clinical grade fully vetted human iPS cell-derived differentiated cells for transplant for a specific patient derived from that patient’s somatic cells (e.g. skin) will cost at least $100,000 and likely far higher, especially in the early days of clinical use of iPS cells. Batch-prepared hESC-based products will be far cheaper.
7. iPS cell timing. It takes time to make iPS cells and even more time to validate and differentiate them prior to hypothetical clinical use. Perhaps as much as 6 months. Thus, for most acute and/or life threatening illnesses and injuries, iPS cells just will not be able to be used in a truly patient specific manner. They can’t compete with batch-prepared, off the shelf hESC-based products that can be used essentially immediately.