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Grow your own stem cells
January 30, 2014 5:31 AM   Subscribe

In this month's issue of Nature, Haruko Obokata and colleagues have made a breakthrough in the field of stem cell research, where they describe a unique cellular reprogramming phenomenon in which skin and blood cells could be converted into stem cells without the need to physically manipulate the nucleus or over-express reprogramming genes. Rather, the researchers subjected them to stress "almost to the point of death", by exposing them to various events including trauma, low oxygen levels and acidic environments. One of these "stressful" situations was simply to bathe the cells in a weak acid solution for about 30 minutes. Within days, the scientists found the cells had not only survived but had also recovered by naturally reverting into a state similar to that of an embryonic stem cell. The research suggests human cells could in future be reprogrammed by the same technique, offering a simpler way to replace damaged cells or grow new organs for sick and injured people.

Some historical context:

In 1958, John Gurdon successfully cloned a frog using intact nuclei from the somatic cells of a Xenopus tadpole.

In 1996, Dolly the sheep was produced by electrofusion of sheep mammary-derived cells with enucleated sheep oocytes (female germline cells), a powerful demonstration of the ability of oocytes to reprogram the DNA of fully differentiated cells back to a stem-cell state.

In 2006, in a seminal study published in Cell, Kazutoshi Takahashi and Shinya Yamanaka managed to reprogram fully differentiated skin cells into stem cells simply by overexpressing four genes. These induced pluripotent stem cells offered new hope to the future of regenerative medicine, since they not only bypassed the ethical and technical problems pertaining to the generation and use of "true" embryonic stem cells, but also the foreseeable rejection issues that would arise when transplanting cells and tissues from one individual to another.

In 2012, Shinya Yamanaka and John Gurdon were awarded the Nobel Prize for Physiology or Medicine for the discovery that mature cells can be converted to stem cell.

In this month's issue of Nature, Haruko Obokata and colleagues have made an arguably similarly significant advance in the field. Says Chris Mason, chair of regenerative medicine bioprocessing at University College London in the linked article: "If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material – the age of personalised medicine would have finally arrived"

Original Nature links for those with access:
Stimulus-triggered fate conversion of somatic cells into pluripotency

Bidirectional developmental potential in reprogrammed cells with acquired pluripotency
posted by kisch mokusch (31 comments total) 25 users marked this as a favorite

 
I'm no scientist, but if a weak acid solution is the key to cells reverting to a more youthful state, then it means humans can de-age 20 years merely by sitting in a bathtub full of orange juice. As your doctor, I recommend you do this immediately.
posted by Greg Nog at 5:41 AM on January 30 [20 favorites]


I don't want to be 15 again though
posted by feckless fecal fear mongering at 5:46 AM on January 30 [2 favorites]


As a kid one of my summer jobs was working for my Dad at his lab cloning plant tissue, specifically opium poppy tissue, for an experiment aimed at trying to figure out where the plant actually synthesized the opium. (It would have been 1984 or something when I did this work.)

Anyway, at the time scientist were just starting to be able to clone what they called the undifferentiated mass or sometimes even the callous of plants. This kind of tissue could later be induced to grow into specialized tissue (e.g. A leaf, stem or root) by cutting a sample if specialized tissue and pressing it into the callous. At that time even though doing these things with plants was actually pretty simple, we thought that doing cloning, cultivating undifferentiated tissue of animals was decades, perhaps centuries away.

It's cool to me to see us moving so quickly. Also neat to see us finding so many sources of stem cells and beat to see the mechanisms we can use to get them cultivated or expressed.
posted by kalessin at 5:58 AM on January 30 [1 favorite]


But what if that makes the cells sad! Oh cells forgive us, we know not what we do.
posted by xarnop at 6:10 AM on January 30 [4 favorites]


Oh, it definitely makes the cells sad. Most of the cells die from the treatment. Also the procedure works best on newborn mouse blood cells. Using adult cells or non-blood cells is far less efficient.

Still, the papers have caused quite a stir in stem cell labs since it seems so simple--everyone in our lab got a copy. I'm compelled to strongly emphasize the "seems" part. Time will tell.
posted by sevenless at 6:52 AM on January 30


humans can de-age 20 years merely by sitting in a bathtub full of orange juice

I just filled my bathtub with orange juice and immersed myself in it for 30 minutes. I don't feel any younger but I do seem to have some super-human orange powers: vitamin C vision, orange peel armor, super-juicing, flight (can't figure out the orange connection, possibly unrelated), zestiness, etc. Apparently now I have to protect the city from some dude who calls himself Captain Scurvy. Overall not recommended, maybe try vinegar.
posted by burnmp3s at 6:55 AM on January 30 [23 favorites]


Next time you have a tooth pulled, or a child loses those first ones, save 'em for the stem cells. www.explorestemcells.co.uk › Stem Cell Sources
posted by chuckiebtoo at 6:56 AM on January 30


I love that on the blue right now, we have something about growing your own stem cells and something about manufacturing your own custom drugs. At some point, we'll be able to grow our very own dealers.
posted by xingcat at 7:00 AM on January 30 [4 favorites]


So ... if I put lots of vinegar on my chips (I'm English), I can get my fat to turn to muscle? Splendid.
posted by dowcrag at 7:00 AM on January 30 [3 favorites]


So we have the groundwork/an explanation for the creation of superheroes! During sufficiently traumatic events, a person's cells revert to stem cells and then adapt by developing whatever feature they need to survive that situation! It's perfect!

Did they try having cells bitten by a radioactive spider? Or dropping radioactive substances on them from a passing truck? Or exposing them to massive doses of gamma radiation?

Or maybe killing their parents in front of them?
posted by Naberius at 7:14 AM on January 30 [3 favorites]


Something something Joker something vat of acid something something.
posted by blue_beetle at 7:29 AM on January 30 [1 favorite]


this person with a spinal cord injury raises a celebratory cup of tea for all this.
posted by angrycat at 7:38 AM on January 30 [17 favorites]


As a kid I was always fascinated by medicines -- mysterious mixtures of stuff that somehow made you better -- and at some point became obsessed with what I thought the discovery process must be. I pictured rooms full of white-coated scientists trying every possible combination of foods and plants and chemicals, all hoping to hit on the right combination. What if you could cure a cold with yellow smartie shells mixed with grass, it's just that none has tried it yet?

Then I learned more about biology and, eventually, drug design, and came to understand the process as something much more rational, considered and prosaic. I spent years studying tiny aspects of mechanisms that contribute to disease that might, one day, suggest a long, difficult path to a cure.

And then some joker says "hey, what if we make these ones hot, and these ones cold, and put these ones in acid, and these ones in a different acid, and, and, and...?" and revolutionises their field. Hmmm.

It's OK, I promise I'm mostly kidding.
posted by metaBugs at 7:48 AM on January 30 [8 favorites]


Still holding out on my shot at immortality.
posted by Sphinx at 8:50 AM on January 30


came to understand the process as something much more rational, considered and prosaic.

or you leave a plate out by accident and let it get mouldy
posted by St. Peepsburg at 8:52 AM on January 30


Rereading my early comment, apologies for all the early morning iPhone typos. The biggest one I should correct is that I believe the name for the undifferentiated mass of plant cells was "callus", not "callous".

The first image in the Wikipedia entry I just linked looks precisely like what my goal was to clone when I worked with Dad. I think the first and only full batch I incubated grew 1 plate of callus out of 12 incubated. Dad could at that time do more like 9 of 12.

At the time the process was just getting worked out. If I remember correctly, the big issues were suitability of and quality of growth medium (which for plants was a nutrient-laden agar base - the vaguely translucent stuff on the bottom of the petri dish) and the sterility of the incubation/inoculation work area.

Speaking of sterility, Dad had managed to fund and purchase a $100,000 sterile laminar flow hood, which was a hooded workbench that kept itself sterile (after initially being sterilized) by keeping a laminar layer of sterilized air flowing in front of the hood, to sweep and keep out undesirable bugs.

Years later he told me how astounded he was when he spoke with a newer grad student who'd achieved the same level of sterility by working within about 2 or 3 feet of a burning Bunsen burner. Apparently the convection cell that a Bunsen burner sets up around itself is very sterile owing to anything living floating in the air getting carbonized in the flame.

I mention all this of course in case someone needs to rebuild civilization and needs a cheap and easy sterile environment to work in in the post-apocalyptic world after the stem cell zombies all eat us for breakfaast.
posted by kalessin at 8:53 AM on January 30 [3 favorites]


Rather, the researchers subjected them to stress "almost to the point of death", by exposing them to various events including trauma, low oxygen levels and acidic environments.

Trauma and low oxygen (at least) are conditions the cells of organs are likely to encounter within living creatures during the ordinary course of injury and disease, so it seems reasonable to see this as the discovery of a mechanism by which organs are repairing themselves when they are damaged.

As such, it may have limited utility in medicine because we are very likely already doing it in the situations where it could be useful.
posted by jamjam at 9:14 AM on January 30 [1 favorite]


Something something Joker something vat of acid something something.

The Joker IS Batman!
posted by vitabellosi at 9:22 AM on January 30 [1 favorite]


As such, it may have limited utility in medicine because we are very likely already doing it in the situations where it could be useful.

Wait so your body already has the capacity to grow new organs and eyes and teeth and a spinal cord when it needs to? You might want to call science and let them know.
posted by crayz at 10:02 AM on January 30


Well it has the potential capacity, possibly. If stem cells are part of the normal healing mechanism for extensive trauma.

I mean Octavia Butler wrote a whole series (starting with Dawn) about how genetic engineering aliens merged with our species primarily due to our other frightening but potentially regenerative biological "talent": cancer.

I am totally unfamiliar with the current research. Do we know if stem cells are in any way similar in mechanism or metabolism to cancer cells?

I know I've read (but don't know if they're currently disproven) evolutionarily-based theories about how cancer could be a mutation of some sort of healing factor.
posted by kalessin at 10:27 AM on January 30


Oops, wrong thread.
posted by Mental Wimp at 10:28 AM on January 30


Ok, the Editor's Summary is pretty accessible:

The fates of the somatic cells that form the bulk of the mammalian body are thought to be largely determined by the time the cellular differentiation processes of development have been completed. Reprogramming in response to environmental stress has been observed in plants but not so far in mammalian cells. Now two manuscripts by Haruko Obokata and colleagues describe an unexpected reprogramming phenomenon, which the authors call stimulus-triggered acquisition of pluripotency (STAP). In STAP, mouse somatic cells such as CD45+ haematopoietic cells are reprogrammed to pluripotency by transient exposure to low pH. Extensive analysis of the molecular features and developmental potential of STAP cells suggests that they represent a unique state of pluripotency — and provide an alternative source of pluripotent cells to the use of transcription factors, as has become routine for induced pluripotent stem cell production.

Also, wonderful use of "sublethal":

We recently discovered an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which we call stimulus-triggered acquisition of pluripotency (STAP). This reprogramming does not require nuclear transfer or genetic manipulation. Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues [...]
posted by RedOrGreen at 11:00 AM on January 30


newborn mouse blood cells

OMG ELIZABETH BATHORY WAS RIGHT
posted by Sara C. at 12:18 PM on January 30


Greg Nog: I'm no scientist, but if a weak acid solution is the key to cells reverting to a more youthful state, then it means humans can de-age 20 years merely by sitting in a bathtub full of orange juice. As your doctor, I recommend you do this immediately.
That's dumb. That will only make your skin youthful.

If you want to enyouthenate everything, you have to bathe all your cells in acid.

Two tabs oughta do it. Three for the older folk. Four if you're Pete Seeger.
posted by IAmBroom at 12:38 AM on January 31 [2 favorites]


From Nature News:

On average, she says, 25% of the cells survive the stress and 30% of those convert to pluripotent cells — already a higher proportion than the roughly 1% conversion rate of iPS cells, which take several weeks to become pluripotent.

If true and if this works in other people's hands, this is pretty amazing. Several labs near mine work with Yamanaka-style iPS cells and while you can do really ground-breaking work that way (including making iPS cells directly from patients and controls), it is an extremely touchy and time-consuming procedure to make them. These yields are ~7-8x higher.
posted by en forme de poire at 8:58 AM on January 31 [1 favorite]


These yields are ~7-8x higher.

And generated more quickly and cheaply. Even if the phenomenon only holds true for mice and not humans, it should still make stem cell research a lot more accessible to not-so-well-supported labs. I too am very keen to see the independent confirmation.
posted by kisch mokusch at 7:20 PM on January 31 [1 favorite]


Yeah, so about that... not looking so great for independent confirmation so far.
posted by en forme de poire at 8:04 PM on February 12 [1 favorite]


That link also contains the wonderful term "stem cell ceviche."
posted by en forme de poire at 8:46 PM on February 12 [2 favorites]


Damnit!

Acid-bath stem-cell study under investigation

A leading Japanese research institute has opened an investigation into a groundbreaking stem-cell study after concerns were raised about its credibility.

The RIKEN centre in Kobe announced on Friday that it is looking into alleged irregularities in the work of biologist Haruko Obokata, who works at the institution. She shot to fame last month as the lead author on two papers published in Nature that demonstrated a simple way to reprogram mature mice cells into an embryonic state by simply applying stress, such as exposure to acid or physical pressure on cell membranes. The RIKEN investigation follows allegations on blog sites about the use of duplicated images in Obokata’s papers, and numerous failed attempts to replicate her results.


Aaaaaagh.
posted by RedOrGreen at 8:47 AM on February 18 [2 favorites]


Also: Acid-bath stem cell results called into question
posted by kisch mokusch at 2:20 PM on February 19 [2 favorites]


Also: Acid-bath stem cell results called into question

This looks pretty bad for this route to stem cells. Too bad. It would have been a revolutionary technology.
posted by Mental Wimp at 4:41 PM on February 19 [1 favorite]


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