Reprogramming of whatever

by Alexey Bersenev on January 2, 2009 · 0 comments

in under discussion

we know very little about how it works…
those cells should be very useful in drug screening and toxicology

Shinya Yamanaka

I like to cite Shinya Yamanaka when i’m writing about iPS and reprogramming, because he always says only few words, but everything is very simple and reliable.

Well, last year (2008) was declared the “Year of the reprogramming” according Science magazine.

I’d like to remind you that reprogramming and creation of human iPS were scientific (#1) and even medical (#9) breakthroughs in 2007 also. Nothing in the scientific world was discussed in 2008 as much as stem cells, reprogramming and iPS, right? If so, I hope I have a chance to get more audience attention to my blog this year.

So what was the 2008 breakthrough in reprogramming? Basically, there are 2 main achievements:
1. the creation of human iPS without oncogenes and retroviruses or even viral-free (many papers and protocols published);
2. creating patient-specific iPS lines

Now I’d like to tell you, my dear reader, a few things that I like about reprogramming and that I don’t like:

I like:
1. It’s really biological magic
Very good example of satisfaction of scientific curiosity.

2. System is remarkably reproducible!
It was done in many labs around the world with quite similar results.

3. Speed and scale of research in the “reprogramming field”
Because it’s going on in many laboratories now with crazy speed and under good financial support, we have a chance to get to know very soon if that a real thing (for practical point of view – disease modeling, drug testing) or bullshit (inapplicable artificial system). Or in other words: should we continue to invest so much time and money in this?

I dislike:
1. System is too artificial and too far from nature
We’ve shown that’s it really works but so what? So far iPS is a transformed cell line, which makes it difficult to use for disease modeling and patient-specific drug testing (point of Shi V. Liu). So embryonic stem cell is still the gold standard (George Daley).

2. Overestimation of therapeutic potential
Every second professor in their talks indicates that this work is remarkable for “new personalized cell therapies” and mass-media multiply everywhere – this is a new therapeutic hope for patients with degenerative diseases. Yamanaka stopped to talk about it long while ago, that’s why i like to cite him.

3. Overestimation of significance by Big scientific journals.
I can’t understand why any second paper from reprogramming/iPS field with BigName at the end of author’s list continue to get Nature/Science/Cell??? It’s too much, really.

4. Mess with terminology: reprogramming and direct transdifferentiation
Basically direct transdifferentiation that Melton’s group did in vivo in 2008 got in “reprogramming” field and ended up in the category “breakthrough of the year”.

Thomas Graf about significance of direct transdifferentiation and difference with reprogramming:

Cell reprogramming involves the generation of ES cells, or cells that closely resemble them. Induced transdifferentiation/lineage conversions, on the other hand, do not seem to go through an iPS cell state, and by that criterion, the two processes are different.

If we can do this directly it would simplify therapeutic protocols tremendously. It is never going to be trivial for a clinic to generate induced pluripotent stem (iPS) cells for a patient and then coax these cells into the cell type they require for cell therapy in large numbers without the danger of producing contaminating cells that might be tumorigenic. If you had a way to do this directly, it would be an enormous advantage.

We have already seen the first spectacular example that it might be possible in the recent paper by Doug Melton where they converted exocrine into islet cells in an animal. So that’s even better, you don’t even have to do any cell culture. If you can do it in a particular organ, you can repair organs in an almost non-invasive way.

I’d like to finish with one more citation of Thomas Graf (I love his interview by Monya Baker!):

Do not join the iPS craze unless you are pretty sure that you have a unique angle or question. Directed transdifferentiation could become a hot new area; it is not yet too crowded.

A 2008 reprogramming round-up
Science magazine video: Reprogramming Cells
Science magazine podcast (mp3)

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