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Stem Cell Breakthrough
August 1, 2008 8:32 PM   Subscribe

Scientists report a breakthrough in stem cell production: Stem cells created from ALS patient and used to make neurons. [Via]
posted by homunculus (39 comments total) 6 users marked this as a favorite

 
What? That can't be right. We're supposed to be using fetal stem cells. Can't anyone think of the children?
posted by Mr.Encyclopedia at 9:05 PM on August 1, 2008


Or the menstrual blood?
posted by Asparagirl at 9:13 PM on August 1, 2008


That can't be right. We're supposed to be using fetal stem cells.

What?
posted by homunculus at 10:07 PM on August 1, 2008


Researchers insert four genes into a patient's cells, reprogramming them into embryonic- like stem cells. These cells, called iPS cells, appear to have the same capability as embryonic stem cells to develop into any type of tissue in the body.

This is incredible news... no way to claim these have souls, right?
posted by Ron Thanagar at 10:21 PM on August 1, 2008 [1 favorite]


I knew those English as a Second Language students would be good for something. All right. Hook them up to machines and start milking them for their stem cells. They can do their grammar lessons from the lab.
posted by Astro Zombie at 10:39 PM on August 1, 2008 [3 favorites]


The reason this is particularly interesting and valuable is that the patient's own cells were being used.

Which may have good sides and bad sides. If there was some genetic reason for the disease being treated, the gene(s) will still be present in the new tissue and could recur.

On the other hand, the cells will be "self" and won't be rejected, so the patient won't have to take immunosuppressives for the rest of his life.

And of course, there's substantive moral objection to using a patient's own cells to cure him.
posted by Class Goat at 11:29 PM on August 1, 2008


Rats. That should have been "There's no substantive moral objection to using a patient's own cells to cure him."
posted by Class Goat at 11:29 PM on August 1, 2008


And of course, there's substantive moral objection to using a patient's own cells to cure him.

I use my own cells to cure myself every day, all day. It's called an immune system.
posted by five fresh fish at 11:34 PM on August 1, 2008


This is about as exciting to the scientific community as a fat man picking his nose. Wake me when they actually learn something rather than generate the first few of many extremely easy to make disease specific cell lines via iPS cells.
posted by available at 12:03 AM on August 2, 2008


Link to original science article:
http://www.sciencemag.org/cgi/content/abstract/1158799
posted by kisch mokusch at 12:09 AM on August 2, 2008


no way to claim these have souls, right?

Time is of the essence (or effluence).
posted by Mblue at 12:09 AM on August 2, 2008


If I die before I'm, say, 300 years old, I'm going to be very very disappointed.
posted by stavrosthewonderchicken at 12:31 AM on August 2, 2008


If I die before stavrosthewonderchicken, I'm going to be very very disappointed.
posted by TwelveTwo at 12:52 AM on August 2, 2008


...in my assassins.
posted by TwelveTwo at 12:52 AM on August 2, 2008 [1 favorite]


Zing!
posted by lumensimus at 1:11 AM on August 2, 2008


Don't encourage me. I'm not maintaining a healthy, respectful discussion by focusing comments on the issues, topics, and facts at hand. Anyway, I like stem cells. I approve of this FPP.
posted by TwelveTwo at 1:28 AM on August 2, 2008


Class Goat - you make a really salient point about the inherent genetic defect in autologous transplantation.

Probably not a cure for type 1 diabetes, but possibly one for type 2? Just make islets instead of motor neurons. Not going to be viable for anything related to autoimmune disorders.

I've been pessimistic about pleuripotent cell-derived nerve cells. I can make an immortalized human embryonic kidney cell kinda-sorta look like neuron in culture.

My proxie isn't working right now but unless they at least stain for pre- and post- synaptic markers and receptors and do some electrophysiology, I'll remain skeptical.
posted by porpoise at 1:41 AM on August 2, 2008


My proxie isn't working right now but unless they at least stain for pre- and post- synaptic markers and receptors and do some electrophysiology, I'll remain skeptical.

I don't think they did that. I can't access the paper proper, but I can access the Supplementary Material, and it looks like they just differentiated them with RA and immunostained them for classic neuron markers.

From the Supplementary Figures:

SUPPLEMENTARY FIGURE S5. iPS cells generated from ALS patients can be differentiated into motor neurons. (A) Schematic of protocol used to direct the differentiation of PS-iPS to motor neurons. EBs derived from iPS cell line A29a were grown for 10 days before treatment with retinoic acid (RA) and a small molecule sonic hedgehog (SHH) signaling agonist. After two weeks of continued suspension culture in the presence of these inductive molecules, EBs were dissociated and cells plated on laminin. After 14 days of maturation, motor neurons were detected by immunocytochemistry for (B-D) HB9, (C) ISLET1 and ISLET2, and (D) ChAT.

SUPPLEMENTARY FIGURE S6. PS-iPS generated motor neurons display characteristic morphology. (A) Long TuJ1 positive neuronal outgrowths are visible with HB9 positive nuclei.

SUPPLEMENTARY FIGURE S7. Patient-specific motor neurons from A29b iPS. Representative images demonstrating neuronal morphology and detection of HB9 encapsulated by TuJ1 stained ß-Tubulin-IIIb expressing neuronal cell bodies and processes.

SUPPLEMENTARY FIGURE S8. The motor neuron markers HB9 and ISL are highly coincident. (A) Images from A29b motor neuron cultures, as from Figure 4, depicting the efficient production of co-positive HB9/ISL motor neurons.

SUPPLEMENTARY FIGURE S9. (B) The co-expression of HB9 and ChAT indicates the cholinergic transmitter status of matured patient-specific iPS derived motor neurons.

posted by kisch mokusch at 2:30 AM on August 2, 2008 [2 favorites]


Maybe you guys could take the stem-cell debate/circle-jerk elsewhere. As usual in cases like this it would be great if someone can read between the lines and break this down a bit further. Just the fact that we now may have a supply of material with which to conduct research into ALS is, to me, absolutely incredible.
posted by docpops at 3:29 AM on August 2, 2008


Maybe you guys could take the stem-cell debate/circle-jerk elsewhere.

No, no, no, you are confusing gametes with zygotes. To get stem-cells you need more than a circle-jerk.
posted by BrotherCaine at 5:19 AM on August 2, 2008


I'm pretty ignorant when it comes to biosci, but could someone explain why they are de-differentiating skin cells rather than a longer lived cell type? I'd think the more often the cell had replicated and/or the shorter the telomeres, the greater the likelihood that ensuing de-differentiated stem cell treatment would eventually result in cancer.
posted by BrotherCaine at 5:30 AM on August 2, 2008


Oh, scratch that, they're just researching right now, not treating.
posted by BrotherCaine at 5:33 AM on August 2, 2008


Porpoise, at the UCSF diabetes patient symposium this year they talked extensively about research into knocking out the auto-immune response in Type I diabetics. I have the feeling that if they combine the current therapies with stem cell research there will be a cure for Type I diabetes. Do a lookup on anti-CD3 if you are interested.
posted by BrotherCaine at 6:11 AM on August 2, 2008


If there was some genetic reason for the disease being treated, the gene(s) will still be present in the new tissue and could recur.

In addition, isn't this nugget also a major design problem? : the technique currently used to create the iPS cells requires adding viruses and genes that can cause cancer.

Is this more of a breakthrough because it's a potentially embryo-less way of obtaining stem cells for further research, or because of the potential to transplant new cells back into the patient to replace dying ones? Both?
posted by Adam_S at 7:26 AM on August 2, 2008


Is this more of a breakthrough because it's a potentially embryo-less way of obtaining stem cells for further research, or because of the potential to transplant new cells back into the patient to replace dying ones? Both?

The former. Your cells are built to not do this for a good reason. Is everyone who gets iPS cells to differentiate into something going to get a science paper?
posted by a robot made out of meat at 8:20 AM on August 2, 2008


I'm working on a play involving a character with ALS, so I've been following the research for a while now. The importance of this discovery is that now the scientists can take these iPS cells and study them in the lab, OUTSIDE of the patient's body. Now they might be able to understand exactly how these cells die, and therefore find how to save them.
posted by condorman at 8:59 AM on August 2, 2008


What kisch mokusch gleaned from the Supplementary Figures is pretty much what is reported in the body of the paper.
posted by Turtles all the way down at 9:13 AM on August 2, 2008


Thanks kisch mokusch! And BrotherCaine, yes, I'm aware of immune regulation in the potential therapy for type I diabetes - it's fascinating stuff but fiddling with the immune system is a tricky thing. Don't want to swap one disease for another (I used to work on chronic GVHD after blood and marrow transplantation). meat robot - getting published in Science and Nature these days involves a little bit of politics in addition to the science, unfortunately.

I'm not denigrating the work, it's very very necessary basic science that needs to be done. But even the authors acknowledge (in the abstract) that it's still a far ways off from using these re-differentiated cells for treatment and even concede that turning iPS into motor neurons has a bit of a "gee whiz" factor. Also, a neuron - to me - is a functioning biological unit*, not just a cell that kinda-sorta looks like a neuron and expresses a handful of neuronal markers.

I wonder what other cell-type specific markers (of non-neuronal cells) these induced "neurons" also express?

*a few important details such as the ability to respond to a variety of environmental and chemotactic cues to grow and migrate, the ability to receive different types of synaptic input, the ability to synapse onto another neuron/cell and communicate with that, and have the machinery to modulate synaptic strength over the long term, &c. Neurons are very very complicated little fellas.
posted by porpoise at 10:58 AM on August 2, 2008 [1 favorite]


This is about as exciting to the scientific community as a fat man picking his nose. Wake me when they actually learn something rather than generate the first few of many extremely easy to make disease specific cell lines via iPS cells.

Without basic science such as this, researchers will never get to make discoveries that are interesting to you.

But we'll look forward to the FPP of "Metafilter Member 'Available' Does The Complicated Science, Claims Researchers Previously Wasting Their Time With Easy Shit."
posted by desuetude at 12:43 PM on August 2, 2008 [1 favorite]


But we'll look forward to the FPP of "Metafilter Member 'Available' Does The Complicated Science, Claims Researchers Previously Wasting Their Time With Easy Shit."

I think that's a funny thing to say to someone who does basic research, especially when their focus is stem cell biology. Maybe I should elaborate so you might appreciate my position, considering I have reviewed a number of fellowships and RO1's in the past year, many of which included proposals for the generation of iPS cells for studying a range of diseases (Marfan's, the generation of cardiovascular progenitors for cardiac repair after MI, hematopoietic stem cell generation, and even ALS). The fact of the matter is that this paper is not even a technical achievement, many other groups have already accomplished this for a wide range of diseases including funny enough ALS. So either they too deserve a Science paper, or people can see this for what it is which is not scientific discovery but who submitted first.

Its great that someone took the time to make these cells, which takes about 6 months from our labs experience, but really where is the important gain (big or small) in the understanding of ALS? If you are a scientist, then I think like me you can understandably be disappointed that this got published in a very high profile journal. If you're not a scientist, I might ask what question these researchers really addressed? Its a motor neuron degeneration disease so obviously motor neurons should be able to be generated by an iPS line made from an ALS patient. Considering genetic association studies have revealed that no one locus is responsible for more than 2% of total cases of ALS do you really think this line has captured the diversity of the disease?

posted by available at 4:34 PM on August 2, 2008


Only truly groundbreaking research should be published? You don't think that the workaday stuff contributes to the body of literature in any way?

I get that you're frustrated that this got published in Science. The peer-review system isn't perfect and certainly isn't without bias, but it's a hell of a lot better than the alternatives, in my opinion.

But I was taken aback by what I felt was a cheap sneering comment, especially since the FPP included the mainstream press (who alternate between not giving a shit about basic research or egregiously misrepresenting it.) Use your powers for good, available.

/not a scientist myself, but I work with them.
posted by desuetude at 5:13 PM on August 2, 2008


Considering genetic association studies have revealed that no one locus is responsible for more than 2% of total cases of ALS do you really think this line has captured the diversity of the disease?

Well, I guess this is the "sexy" factor for this paper - one clinical camp thinks that individually targeted therapy is going to be The Next Big Thing (if you're a cynic, think of it as some people who want to charge some very rich old folks a lot of money to cure their specific disease). They show that you can (potentially... potentially, I'm not convinced that it's a neuron) model an individual's disease and throw a bunch of different therapies at it. Whichever one works best in the culture dish gets applied to the patient.

I'm surprised that Science took this up, and not Nature.
posted by porpoise at 5:14 PM on August 2, 2008


desuetude - available isn't railing against the fact that this study got published at all but that it got published in Science.

Science is one of those "high impact factor" journals. They make careers for people, either getting hired/tenure or getting more funding. There's probably some politicking going on behind the scenes. Basic researchers are, of course, going to be disappointed that a clinical group gets a Science publication where another basic lab having been able to do exactly the same thing first and for longer's finding would not have been accepted to be reviewed for publication in Science - especially when these guys are going to be fighting for the same ever-more-limited funding in the future but they've got a Science pub to wave in grant reviewers' faces.
posted by porpoise at 5:21 PM on August 2, 2008


Believe me desuetude, I wouldn't be able to have a career in science if I didn't think small everyday discoveries contribute to the advancement of science and our understanding of the world. My job would be way too depressing otherwise.

And I am in no way admonishing peer review, even though our lab has been burned repeatedly by anonymous reviewers holding up our submissions until they can finish and submit their coincidently identical experiments (the latest published next to our work in Nature one month ago). I get that in order to maintain a high impact in the public and scientific forum, these journals must accept less than stellar work if it makes headlines.

Granted I should have left out the second part of my comment, it does not do well to ridicule another's opinion.
posted by available at 7:20 PM on August 2, 2008 [1 favorite]


I'm surprised that Science took this up, and not Nature.

Maybe they submitted to Science first (I've known researchers to go there before Nature). Or perhaps they simply have a good relationship with Science's editor.

Talking of scientists whose careers are made by publications in high IF journals: Kevin Eggan, the corresponding author on this paper, has published 5 times in Nature and 5 times in Science in the last 8 years (for which he was first author on 3, and final author on 2). I don't think he'll have to worry about funding for a while, even in today's climate.
posted by kisch mokusch at 7:37 PM on August 2, 2008


Normally I would say (to all you researchers arguing upthread) that you should quit bickering and get back to researching so that you can find a cure for my dad's Lewy-body Dementia, but he died yesterday morning from it, so by all means please do continue to yammer on about who should have their careers made by what publication.

what? what did I say?
posted by davejay at 11:28 PM on August 2, 2008


Davejay, I'm sorry to hear about your dad.

However, my opinion is that most researchers would love to concentrate on the science and ignore the politics of the publishing world, but the researchers who can't play politics and/or self aggrandize probably quickly lose funding. Like it or not, funding, petty politics and grant chasing are going to be as important as basic research for science unless scientists can make the business of science publishing extraordinarily transparent and self-regulating.

I'm hoping openmedicine.ca and other efforts will transform the sci/med publication industry, but I'm not holding my breath.
posted by BrotherCaine at 5:06 AM on August 3, 2008


It's a shame about your dad, Davejay.

But do you really think you're the only one whose watched their father or mother or sister or brother die by one of these horrible diseases. Guess the only difference between you and essentially all of my colleagues is that we got up off our ass and did something about it. Let's hope you might follow that example.
posted by available at 10:13 PM on August 3, 2008


Hey, is this where I sign up for the assholes competition?
posted by five fresh fish at 10:36 PM on August 3, 2008


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