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Tuesday, November 20, 2007

A Gigantic Breakthrough in Stem Cell Research

posted by on November 20 at 12:45 PM

Human%20iPS%20SSEA4.jpg
(Image from Takahashi et al., Induction of Pluripotent Cell form Adult Human Fibroblasts by Defined Factors, Cell (2007), doi:10.1016/j.cell.2007.11.019)

Okay. Now I believe.

Two groups working independently—Dr. Yamanaka’s lab in Japan and Dr. Thomson’s Lab in Wisconsin—have converted human cells into embryonic stem cell-like cells. This tremendous accomplishment is on par with the initial creation of human embryonic stem cells about ten years ago, the completion of the human genome project and development of gene knockdown technology.

With this trick, skin cells can be converted into embryonic stem cell-like cells that can become any cell type in the body, including difficult to acquire human heart and brain cells.

I’ve written about this technique rather skeptically in the past. All of the previous work was with mouse cells. Now with two groups independently showing it works also with human cells, I’m pretty convinced. Yes, these two papers are pretty sloppy. The Thompson one reads like it was written over the weekend and the Yamanaka paper has a few glaring flaws. Still, the evidence has tipped in this case.

If you want a more detailed scientific breakdown of what these groups did, keep reading here. Else, what this all means is after the jump.

Why are these Induced Pluripotent cells (iPS) so exciting?

The ability to make patient- or disease-specific stem cells should give a boost our unraveling of how complex combinations of genes cause illness or change responses to medications--particularly in combination with the human genome project and the ability to selectively shut off genes in cultured cells through RNA interference.

Let's say you have two patients, one who responds to a cardiac drug and another who doesn't. If you want to figure out why, you could now pluck some skin cells from each patient, and create iPS cells from each. In turn, iPS cells can be differentiated into heart cells (or blood vessel cells, or neurons, or liver cells and so on.) The heart cells can then be tested with the drug in a dish. Genetic differences between the two sets of heart cells--both in what genes each patient has, as well as which are on in their heart cells--can be determined and compared to the reference human genome sequence. The likely candidate genes can be turned off to figure out which ones are required.

Right now, iPS cells would be too dangerous to treat patients. Still, with a few relatively straightforward improvements, iPS cells could easily be a new cell source for treatments.Thus far, the techniques developed for embryonic stem cells--how to turn them into brain or heart cells--seem to work for iPS cells. That's fantastic news. New heart cells made from iPS cells--all from a skin stem cell plucked from the patient--could replace the billion or so lost in a heart attack, for example.

The clinical medicine stuff is pure speculation. The impact on modern molecular biology of this technique--if it hold true; please hold true--is hard to understate. I'm excited. You should be too.

RSS icon Comments

1

"...initial creation of human embryonic stem cells 10 years ago.."

Have we actually created them?

Posted by Lake | November 20, 2007 1:04 PM
2

Why must Science always put the good bits after the jump? None of the other niche writers (Theater, Art, Politics) feels the need for such timidity. Post forcefully, Science!

Posted by Chip | November 20, 2007 1:38 PM
3

If only we'd kept Terri Schiavo alive long enough to see this day.

Posted by Moltarr | November 20, 2007 2:01 PM
4

Actually, this is a viral insertion method, and you only get around 100 proto stem-cells out of around 1 million skin cells.

And it's of limited use as the science reporter at the Washington Post had to admit when I and others interrogated him today about it.

Don't worry, all the religious freaks will hate this too.

Posted by Will in Seattle | November 20, 2007 2:02 PM
5

the next leap will be tricorders & those little flashy lights they affix to your temples.

Posted by max solomon | November 20, 2007 2:05 PM
6

Hm...

Wouldn't obstruct replication but it does give rise to an error in replication so that the newly formed DNA strand carries with it a mutation and you've got a virus again... but this, all of this is academic.

Posted by Tyrell | November 20, 2007 2:08 PM
7

@Will: I've made this same efficiency criticism in the past. It's not great, but good enough(tm).

And, like I said, with viral insertion there is no way this could be used clinically. For in vitro work, I'd trust it. And, with tat-mediated protein transduction, I have a feeling this would work.

@Chip: You made my day with that comment.

Posted by Jonathan Golob | November 20, 2007 2:20 PM
8

Previously here.

Posted by Ryan | November 20, 2007 2:21 PM
9

There still seems so much to work out re: silencing the genetic insertions, the health of the resultant daughters through multiple passages after genomic restructuring, chromatin remodelling, etc.--It's hard to believe that these cells could become viable for use after the transformation to stem cell-like and then re-differentiation. On paper it seems like a grand breakthrough, but so did gene therapy once upon a time...

Posted by Mittens Schrodinger | November 20, 2007 2:26 PM
10

I apologize for the tasteless and cruel remark about Terri Schiavo.

Posted by Moltarr | November 20, 2007 3:13 PM
11

@6,@7 - I know, the mutation factor plus the lack of replication, and clinical non-usage makes it only a stopgap solution.

Meanwhile all the bio research money is flooding offshore.

Way to kill America, radical fundies!

Posted by Will in Seattle | November 20, 2007 4:18 PM
12

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13

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