February 15, 2010
Embryonic Still Beat Induced Pluripotent Stem Cells

Some U Wisc Madison researchers compared induced pluripotent stem cells (iPS cells - made from reprogrammed adult cells reprogrammed) to embryonic stem cells and find embryonic stem cells become other cell types more efficiently. Techniques to make iPS cells still need additional improvement.

MADISON The great promise of induced pluripotent stem cells is that the all-purpose cells seem capable of performing all the same tricks as embryonic stem cells, but without the controversy.

However, a new study published this week (Feb. 15) in the Proceedings of the National Academy of Sciences comparing the ability of induced cells and embryonic cells to morph into the cells of the brain has found that induced cells even those free of the genetic factors used to program their all-purpose qualities differentiate less efficiently and faithfully than their embryonic counterparts.

The finding that induced cells are less predictable means there are more kinks to work out before they can be used reliably in a clinical setting, says Su-Chun Zhang, the senior author of the new study and a professor in the University of Wisconsin-Madison School of Medicine and Public Health.

"Embryonic stem cells can pretty much be predicted," says Zhang. "Induced cells cannot. That means that at this point there is still some work to be done to generate ideal induced pluripotent stem cells for application."

The biggest advantage of iPS cells is that they can be made from each person's adult cells. So they avoid immuno-rejection problems. Plus, they just feel less alien. They are your own cells. I also think there's another practical benefit I've yet to see mentioned: iPS cells made into neural stem cells are less likely to change your personality by producing neurons that'll behave differently for genetic reasons.

Dr. Zhang does not expect this advantage of embryonic stem cells to last for long.

Despite their unpredictability, Zhang notes that induced stem cells can still be used to make pure populations of specific types of cells, making them useful for some applications such as testing potential new drugs for efficacy and toxicity. He also noted that the limitations identified by his group are technical issues likely to be resolved relatively quickly.

"It appears to be a technical issue," he says. "Technical things can usually be overcome."

Many researchers are quite busy working on improved techniques for making iPS cells. For example, some Stanford researchers have just developed a safer and easier way to make induced pluripotent stem cells.

STANFORD, Calif. - Tiny circles of DNA are the key to a new and easier way to transform stem cells from human fat into induced pluripotent stem cells for use in regenerative medicine, say scientists at the Stanford University School of Medicine. Unlike other commonly used techniques, the method, which is based on standard molecular biology practices, does not use viruses to introduce genes into the cells or permanently alter a cell's genome.

It is the first example of reprogramming adult cells to pluripotency in this manner, and is hailed by the researchers as a major step toward the use of such cells in humans. They hope that the ease of the technique and its relative safety will smooth its way through the necessary FDA approval process.

"This technique is not only safer, it's relatively simple," said Stanford surgery professor Michael Longaker, MD, and co-author of the paper. "It will be a relatively straightforward process for labs around the world to begin using this technique. We are moving toward clinically applicable regenerative medicine."

Lowly fat cells harnessed to a higher purpose.

The Stanford researchers used the so-called minicircles - rings of DNA about one-half the size of those usually used to reprogram cell - to induce pluripotency in stem cells from human fat.

Share |      Randall Parker, 2010 February 15 09:59 PM  Biotech Stem Cells

kurt9 said at February 16, 2010 8:43 AM:

The problem is cellular aging and it is a technical problem. I do not think it will take a long time to solve it. Once they can rejuvenate the iPS's, then they will be as good as the embryonic stem cells. Aging is a problem that needs fixing anyways. I don't think we have robust regeneration without robust rejuvenation anyways.

Bob Badour said at February 16, 2010 9:33 AM:

I am not as certain the problem is cellular aging, but I agree it is a technical problem. Then again, I have not researched this at all so YMMV.

My guess: The technical problem simply amounts to granularity of control. We have iPS when someone did something really simple nobody else had tried because "it can't possibly be that simple." Lo and behold, it worked. Now we are discovering "Well, it sorta worked."

It sounds like most of the cells go in the desired direction but a few miss the mark a little. I suspect we have a choice: Improve control to make all the cells hit the exact mark, or improve control to filter out the cells that might miss it a little.

I am not surprised by the result.

LAG said at February 16, 2010 9:43 AM:

I note that you do not address the study methodology. Could it be a little early to say that this represents a significant shift? After all, we've learned recently that "peer-review" and "published in a reputable journal" does not always mean what it should. (See the recent Lancet-vaccine study retractions and the AGW emails.)

Lono said at February 16, 2010 10:01 AM:

As someone who privately banked his children's cord blood - I must say I am discouraged at the lack of enthusiasm in - at the very least - publicly banking cord blood for research.

Supposedly there's some liability issue there with blood loss - but the risk seems beyond minor in children born of a healthy weight - I know I watched and didn't feel that any of my children were at risk by the proceedure.

I do hope that these issues with the IPS's can be solved - but I fear it may take decades or more to do so...

th said at February 16, 2010 4:01 PM:

There is a need for anti-rejection drugs in many cases of embryonic stem cell treatments, wouldn't that put embryonic ultimately at a disadvantage? This study doesn't quantify the advantages over the complications, its like saying coal is better at producing electricity, but ignores the mercury, yuk yuk.

Bob Badour said at February 16, 2010 4:44 PM:


If one uses iPS to treat Alzheimers, for example, one would not want the cells to grow a thumb inside one's brain--especially a thumb the body won't kill off as an invader. That makes unpredictable cells entirely unusable in therapy regardless of reduced rejection risks.

th said at February 16, 2010 5:26 PM:

badour, it's better than tumors, warning large blocks of print, no pictures, http://www.physorg.com/news160816468.html

Bob Badour said at February 16, 2010 5:59 PM:

Pictures are optional. Links are important. Both your post and the linked article have them. Well done!

Eh, tumor/thumb--about the same thing I suppose. But as your linked article suggests, the embryonic stem cell to tumor pathway is reasonably well understood. Again, though, the solution is a technical one and pretty-much the same: granularity of control. It's just that a single gene expressed in embryonic stem cells seems to control the tumor pathway so controlling that one gene might solve the problem.

PacRim Jim said at February 16, 2010 10:12 PM:

The more we learn about the human system, the more we realize we don't know, and will not benefit much for decades. Too bad for us.

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