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Friday, March 24, 2006

Stem Cell problem solved?
Nature brings us an excellent paper this week on creating embryonic stem cell-like cultures from adult mouse testes. Here is a lay article on the findings.

This paper is great. To sum up:
1. Spermatogonial cells were purified from mouse seminiferous tubules by digesting with enzymes, then culturing with or without MEF's and LIF (aka mouse ESC medium) to make embryonic stem cell like lines. Take home message: this is a very simple technique.
2. Cells were shown in vitro in embryoid body experiments to be pluripotent. Take home message: these cells are capable of making any type of adult cell.
3. Cells were injected into mouse blastocysts to make chimeras, which were then capable of germ line transmission of the original stem cell genotype. Take home message: this is the ultimate totipotency experiment. These are truly a powerful cell line capable of making all kinds of adult tissues and even transmission of genotype to successive generations of animals.

This is the first paper I've seen that truly bypasses embryonic stem cell ethical limitations. That bullshit about limiting ES cell potential based on making lines that lacked the ability to make embryos was just sophistry to appease those who believe in ensoulment at conception. Finally, here is a technique for making embryonic stem cells, from adults, that are syngenic with the host they come from, without destruction of embryos. Maybe we can shut the damn right-wingers up now and get ES cell research rolling in this country, but only if we can repeat this result using cells from human testicular biopsy or cadaverous donation.

Now, the downside of course, is that the ES cells are made from testicular spermatogenic cells. So, the ladies are definitely not winning out here. However, it is likely that enough ES lines could be made that most immunologic problems could be bypassed by creating lines representing all possible combinations of histocompatability, rather than making them from every single individual that needs them.

What do my fellow scientists think? Is this a good paper or what?

**update** I wrote a Diary over at Daily Kos on the paper.


Another Anonymous Poster said...

Intriguing method of getting around the ethical issues (until some new whackjob comes up with some other mis-read of the bible to suggest that encapsulation of the soul is somehow tied to the acrosome or something). But one MAJOR beef with the paper:

Testicular cells (2–3 [10^7] per mouse) were isolated from Stra8–enhanced green fluorescent protein (EGFP)/Rosa26 adult mice

Take home message: They tied a fluorescent protein to a protein only expressed in the cells they wanted, then sucked up a whole bunch of mouse testes and only grew up the ones that glowed. I'll be damned if I let someone stick a lentivirus-GFP needle up my peehole

11:19 PM, March 24, 2006

Another Anonymous Poster said...

OK, I read it a bit more. It sounds like they were able to figure out how to get them from non-GFP mice. But their success rate was much lower. Supposing that success rate will rise with more practice, I retract my previous comment (except the part about needles and pee-holes. That still is a no-no)

11:23 PM, March 24, 2006

Rev. Dr. said...

That's true, there is a need for isolation of a specific cell type that was optimized using a transgenic.

However, it would be possible to extract seminiferous tubules from an adult human, then transiently transfect a promoter-reporter to identify the cells of interest, and purify by FACS. Alternatively, they might by able to purify using a noninvasive technique like sorting for the SSEA epitopes on the outside of cells.

Either way, an intriguing paper that shows that cells of great potential exist in the adult. Now it is a matter of developing safe and reliable methods of purifying them from adult humans.

It would be nice, from a political perspective, to be able to use these as an example of why the ES cell debate should be irrelevent to politics and hopefully eliminate it as a wedge issue in the coming election.

12:09 AM, March 25, 2006

Comandante Agí said...

Give up blog...I dig your name. You sound like a defeatist at heart.

3:24 PM, March 25, 2006

Rev. Dr. said...

We are similar in message Comandante. Our message only differs in that we think when Republicans win, the blue states also inadvertantly win. Republicanism tends to be far worse for red states than blue states, and in some ways highly beneficial to the blues, since they generate a majority of the country's income, GDP, etc. In a way, the worst thing the Republicans can do for their standing in the red states is to win, and inflict Republicanism on their constituency. Like the bankruptcy bill, Katrina incompetence, environmental mismanagement, etc., all these things impact red states far worse than blue states (see our many maps).

So, let the Republicans shoot themselves in the foot, see if we care. We'll just point out how you're only screwing yourself if you vote for these guys.

5:55 PM, March 25, 2006

Murky Thoughts said...

"shows that cells of great potential exist in the adult."

Well, they had to exist, else no offspring. It's more about where we're to find them, and conceptually the germ line ought to have been the first place we looked. I guess it's all a matter of practicalities. Finding an omnipotent cell you can hand-cuff and bring out alive.

9:39 PM, March 26, 2006

Rev. Dr. said...

"conceptually the germ line ought to have been the first place we looked."

There was no guarantee that cells like these would be found, or germ cells would have been a good place to find them Murky.

It was quite likely that despite being capapble of generating an endless supply of sperm, these cells would not have been capable of generating other tissue types with great efficacy. A similar problem was found with hematopoietic stem cells, which produce all the different cells in your blood your entire life, and therefore must stay fairly undifferentiated. These cells are great at making blood, but recent studies have called into question their ability to transdifferentiate into other tissues and no study showed a similar plasticity with ES cells or these maGSC.

It would have been entirely possible that sperm-producing germ cells were undifferentiated enough to continue producing sperm for your entire life, but not undifferentiated enough to make all other tissues. These cells are quite a surprise to the field.

3:04 PM, March 27, 2006


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