November 28, 2020

The Niche

Knoepfler lab stem cell blog

The Inside Scoop on iPS cells early in 2011

It’s been more than 4 years since Shinya Yamanaka published the remarkable finding that his lab could transform or “reprogram” regular cells called fibroblasts into a very unique state that was quite similar to that of embryonic stem cells (ESC).  Yamanaka called these new cells “iPS cells” for induced pluripotent stem cells.

Since that time, the discovery of iPS cells along with the accompanying revolutionary notion that cellular differentiation is a readily reversible state, took the field by firestorm. The number of publications in this new iPS cell field exploded with seemingly important new discoveries coming one after another. There was talk of “no longer needing” ESC anymore. There was talk of the amazing patient-specific therapies that were certain to be developed using iPS cells.

Where do things stand today?

There’s been a lot of buzz just in the last week or so about some recent papers on iPS cells. There was even a USA Today article day before yesterday by Dan Vergano on this topic (quite well written and interesting) suggesting the strong level of mainstream interest in iPS cells. Amy Adams over at CIRM has an interesting take on the current state of the iPS cell field and the USA Today article.

So what’s the scoop on iPS cells?

Research suggests five key conclusions about iPS cells that at this point early in 2011 need to be accepted as likely being facts that are unlikely to change (no matter how much the field is being a roller coaster):

  1. iPS cells are only similar to ESC. Not identical and probably not even close to identical. As we posted last week, what this means is that iPS cells are not going to replace ES cells. iPS cells are still more similar to ESC than they are to their “parental” fibroblasts from which they were made, but there are many differences between iPS cells and ESC including gene expression and DNA methylation and probably many other elements as well. Some of these differences are “memories” of the starting cells from which the iPS cells were made, while some of the changes are likely random, and finally some of the differences are iPS cell specific. Prediction: most likely no matter how good the field gets at making iPS cells using evolving methods, iPS cells will never be the same as ESC and will not be close enough to have quite the same functions. But the good news is that iPS cells do not have to be identical to ESC to be incredibly useful.
  2. iPS cells have mutations in their DNA that are linked to cancer. We discussed before the incredibly important and worrisome finding by the Loring group that iPS cells contain numerous small mutations in their DNA that are of a nature that are seriously problematic for two reasons. First, the mutations are so small that conventional tests (karyotyping) would miss them. Second, all the changes would appear to be pro-cancer. The reprogramming process is a stressful one and it is not surprising that iPS cells acquire mutations. In fact, these mutations may enhance the efficiency of the iPS cell production process. What this study indicates is that it is not good enough to develop efficient, non-genetic methods to make iPS cells. As a field we also need to develop new methods that preserve the genomic integrity of the cells. It is also important to point out that ESC also contain mutations in their DNA that likely arise during their culturing, but a key difference is that the mutations occur more frequently in iPS cells and could even be intrinsic to the process of making iPS cells.
  3. iPS cells are more expensive. As we blogged before, any patient-specific therapy based on iPS cells will always be dramatically more expensive than the same kind of therapy made using batch prepared hESC.
  4. iPS cells cannot be used for immediate, patient-specific treatment of acute disease states. iPS cells have to be made and validated for each patient. As we previously discussed this means that they cannot be used as patient specific therapies in acute injury situations such as spinal cord injury, heart attack, stroke, etc.
  5. iPS cells are the most powerful disease modeling tool ever.

Of course iPS cells have the singular advantage over ESC that any iPS cell therapy will be patient specific and not require immunosuppression.

Hang onto your hat as the field zooms through 2011!