Successful Stem Cell Replacement of Windpipe

thepacketmaster writes "In what is being hailed as a medical milestone, CNN reports a woman suffering from long-term tuberculosis had her lower trachea and bronchial tube replaced by tissue grown from her own stem cells. A team from the universities of Barcelona, Spain; Bristol, England; and Padua and Milan, Italy, decided to go ahead with the surgery instead of having to remove her left lung. The operation, reported Wednesday in the British medical journal The Lancet, has been hailed as a major leap for medicine that could offer new hope for patients suffering from serious illness."

!embryonic

I just feel like I should point this out before someone decides to go on a rant about embryonic SC.

Re:

which makes a reasonable argument against doing something morally questionable and that upsets lots of people, if you can get the same or better resaults without it.

Re:!embryonic

There's nothing morally questionable about using embryonic stem cells, and just because it upsets certain people doesn't make it so.

Re:!embryonic

Humm. So you decide what is moral and not for the planet?
Interesting.....

Re:!embryonic

If you believe that a dozen undifferentiated cells constitute a human being, that's your problem.

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I'm a biologist. I consider an undifferentiated ball of frog cells at the equivalent stage a frog individual. Later this week my students will be using corn kernals in a genetics experiment, because they are individual corn plants. Why make an exception for humans? Now, you can argue about wheather undeveloped humans deserve protection, but that they are human on a basic level isn't at issue.

Re:!embryonic

Why make an exception for humans?

Well, I think it's the other side that's making an exception for humans. The only time anyone has a problem with harvesting ES cells is when it's from a human blastula. "Human" means more than a genetic identity. It's not illogical to say a human blastula may not have human rights, because it's not a "Human" in that sense, even though biologically it is an individual human embryo.

I'm not endorsing that view, for the record.

Re:!embryonic

That is part of why I doubt it, especially since we are talking about mammals & not amphibians, so they don't have "equivelant" stages

Way off. Embryology is very heavily conserved, such that while there are clear differences, there are also clear similarities. An egg gets fertilized to make a one cell stage, cell division makes a hollow space called the blastula stage, the part that becomes the embryo is one cell layer thick. A pocket forms that becomes the gut, that's the gastrula stage. The part of the embryo that becomes the central nervous system makes a tube, that's the neurula stage.

After that point, things start to diverge more, but up until that point the two do have the same stages.

Here are some pictures of blastulas.

http://www.bootstrike.com/Genetics/StemCells/images/human_blastocyst.jpg [bootstrike.com]

http://porpax.bio.miami.edu/~cmallery/150/devel/human_blastula_removed.gif [miami.edu]

http://www.fotosearch.com/comp/PDS/PDS139/microscopic-image-frog_~AA003891.jpg [fotosearch.com]

http://abacus.bates.edu/~ganderso/biology/electron/frog_blastula_composite_image_x350.gif [bates.edu]

As you can see, quite similar. There are certainly equivalent stages.

Here's a wiki page on "embryo" (http://en.wikipedia.org/wiki/Embryo) Notice it says just "animals," many places and doesn't specify which species? It's not laziness.

Maybe you should take his class?

Re:!embryonic

Humm. So you decide what is moral and not for the planet?
Interesting.....

I'm going to wait to see who actually attempts to impose their opinion on someone else by either requiring or prohibiting some action before I say who thinks they decide what is moral and not for the planet.

Oh that's right, I don't have to wait.

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I know I'm probably going to get modded down for this, but it needs to be said:

The only thing "questionable" about Wonkette saying what she said, is the question of how hard Wonkette should be Donkey Punched for saying something like that about somebody else's baby.

I don't care what your political affiliations are, that is just VILE to say that someone's baby wishes they were aborted. I would expect that on /b/. Not from Wonkette.

(Or maybe I SHOULD expect it. Is her site that bad on a regular basis?)

Ok,

Re:!embryonic

which makes a reasonable argument against doing something morally questionable and that upsets lots of people, if you can get the same or better resaults without it.

For specific areas where adult stem cells make sense and indeed have advantages that hardly needs saying.

Of course you have to acknowledge that embryonic stem cells are different and may provide viable treatments in areas where adult stem cells won't work for some reason.

Re:!embryonic

From what some friends of mine at Bristol Uni have been saying, yes this was done with non-embryonic stem cells, but embryonic stem cells would raise the likelihood of success in such cases as they are more likely to adapt to the required level.

And as to whether or not usage of embryonic stem cells is morally questionable, doesn't that depend on a huge set of variables, such as how the cells are harvested (you can save embryonic stem cells from the birth of a living baby for example), and your own personal beliefs?

Re:!embryonic

but embryonic stem cells would raise the likelihood of success in such cases as they are more likely to adapt to the required level.

IANAB (I am not a biologist), but if the possibility set of the patient-harvested polypotent stem cells include trachea cells, I don't see why you would need pluripotent stem cells in order for it to be a "success"?

Sadly, your friends are wrong in that if embryonic stem cells had been used in this case, that it somehow would have had a higher chance of success. The very fact that the safer and stabler ASCs (adult stem cells) were used in this operation means that the patient won't reject the organ, and the patient won't get cancer. Embryonic stem cells are too unstable in their pluripotency for them to be usable, and always go cancerous (tumor rates is one of the measures that is used to determine how well the embryonic cells have been accepted by the test mice/rats -- more tumors means that more embryonic cells lived).

you can save embryonic stem cells from the birth of a living baby for example

Sorry, but you cannot harvest truly pluripotent cells without destroying the embryo. You can get polypotent ASCs that are very nearly the equivalent of pluripotent embryonic stem cells by using cord blood stem cells, but you cannot actually gain pluripotent stem cells without destroying the living organism.

This is why many people (such as myself) are truly puzzled as to why so many people aren't more excited about ASC research -- it is usable today, and the cancer and rejection risks are so much lower than ESCs. As you noted, ASCs harvested from live births through cord blood have more than enough polypotency to treat even many neurological disorders, and they are far superior in their cancer-potential-stability.

Re:!embryonic

Therapeutic cloning has a host of problems all its own -- in addition to the fact that "there is no such thing as a normal clone", the large number of donor embryos that would be required for ever person treated. We have a limited supply of unused living human embryos that we've built up over the years through IVF treatments, but if therapeutic cloning became widespread, there's no way IVF surplus would keep up with the demand. Harvesting aborted humans is another option, but that wouldn't work so well for the cloning part since the aborted organism is largely dead, and is often aborted later on in the development cycle, when performing a wholesale cloning operation is no longer feasible (though I've heard things about some clinics being able to offset costs by selling aborted human embryonic biomatter for research).

Cord blood is a great way to get near-pluripotent ASCs that still maintain most of an ESC's potentiality, but have increased availability and the added stability of being further on down the specialization line. Increased supply means increased odds of finding a matching donor (similar to how bone marrow transplants are done today).

Seems like Adult stem cells are the way to go.

No rejection and lots of progress. This is really great news.

A step toward donorless transplants?

FTA:

To create the new windpipe, the team took a seven-centimeter (2.75-inch) segment of trachea from a 51-year-old who had died. Over a six-week period, the team then removed all the cells from the donor trachea, because those cells could lead to rejection of the organ after transplant.

While this procedure still does require a donor organ, it basically only uses the donor as a collagen framework to grow the patient's cells into.

Could the next step be fabricating the collagen frame, perhaps through 3D printing?

Re:A step toward donorless transplants?

So what you're saying is, I can print out my new and improved wang frame, coat it with my special sauce, wait a month or so, and then take it with me to the doctor's office to get it installed?

SWEET!

Re:A step toward donorless transplants?

'Meat' Printer: ~$2 million dollars from digikey
Wang Frame: $1.89 at wal-mart (sizes may vary)
Special Sauce: 2 minutes?
Doctor's visit: $200 thousand dollars

Scaring the shit out of your woman in the middle of the night with your new found creation called "beast": Priceless...

Collagen matrix

I found this part at least as interesting as the stem cells:

To create the new windpipe, the team took a seven-centimeter (2.75-inch) segment of trachea from a 51-year-old who had died. Over a six-week period, the team then removed all the cells from the donor trachea, because those cells could lead to rejection of the organ after transplant.

All that remained of the donor's stripped-down trachea was a matrix of collagen, a sort of scaffolding onto which the team then put Castillo's own stem cells -- along with cells taken from a healthy part of her trachea.

So there's still a donor involved, but there's less risk of rejection. We're still a ways from growing sophisticated organs from scratch, but this is an interesting implementation detail.

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Indeed, and what's more, the donation was sort of out of convinience, not necessity (sorta... read on.)

The extracellular matrix that the body makes for its own tissues is pretty complex, I have no idea what our capabilities are as far as artificially producing that, but I would guess we're years off from being able to make a good scaffold in a dish. But it shouldn't be impossible forever. At some point, we should be able to make a scaffold from scratch and then populate them with your stem cells, or maybe

slashdotters and their interests...

Somehow, I figured lonely slashdotters would be more interested in this article: Using Stem Cells for Breast Enhancement [wbztv.com]

... which frankly, strikes me as dangerous. If they're replicating stem cells from people who are already at high risk of breast cancer, doesn't that increase it even more (more generations == shorter telomeres)?

-l

Re:slashdotters and their interests...

If they're replicating stem cells from people who are already at high risk of breast cancer, doesn't that increase it even more (more generations == shorter telomeres)?

Not really. Stem cells, like most cancer cells, produce telomerase and tend to have significantly longer telomeres than surrounding tissue. While this declines slowly with age, the cells in waist fat should be no more dangerous than those in breast fat in the same person.

Oh, and I'm not aware of any definitive link between breast size and cancer risk, so I have no idea if transferring fat from the waist -- who hears talk of belly fat cancer? -- to the breasts poses ay risk in itself. I doubt it, though.

New and interesting, but over hyped

I have been listening to this story being hyped in the news all day, but it doesn't deserve quite that much attention. While this is a "great case" that most surgeons would appreciate, and a great outcome for the patient, the CNN report (and NPR and others) does what lay media generally do with medical reports - over-dramatize yesterday's news. This is an evolutionary case based on established surgical technologies which have been validated over the past 12 years, not a revolutionary implementation of new science. And regardless if you have any thoughts or opinions about embryonic stem cell research, this is not an embryonic case, it is just the use of autogenous cells to repopulate a regenerative biomatrix.

This is the "new surgery" of the 21st century, a move toward live engineering of living tissues rather than using alloplastic implants. Much of this new surgery is done strictly in situ, inserting an implant, and letting pluripotential cells circulating through the host find the implant and then reorganize themselves into a mature tissue. This works well with connective tissue matrices that will support the ingrowth of "connective tissue cells" derived from the embryonic mesoderm. The items available to surgeons are manufactured matrices such as Integra (Integra Life Sciences, New Jersey), and cadaveric matrices, usually dermis (of human, bovine, porcine, and equine origin, eg from LifeCell, Ethicon, TEI Biosciences, et al). Simply put, we implant these materials to reconstruct dermis, fascias, ligaments, and various skeletal and mesenchymal structures, and human host cells find them and make new living dermis-fascia-ligaments-etc. This works extremely well for reconstruction of skin and musculoskeletal structures. Not much progress has been made yet on the generation of glands and organs (which require function specific epithelial or ecto-entodermal cells).

These technologies and procedures have been a part of regular surgical practice since about 1996. Make no mistake about it - the tracheo-bronchial reconstruction you read about is a great case, but it is just a progressive implementation of existing concepts and methods to a wider range of diseases and indications. There will be more and more and more of this is the coming decades. In fact, existing regenerative materials could have easily made a new trachea-like conduit, avoiding the need for a human anatomical gift or organ donation, except for one thing . . .

The trachea and bronchi need a special architecture to avoid collapse. Because of the Bernoulli principle, these conduits could collapse during inspiration, so nature prevents that by having these pipes surrounded by semi-rigid cartilage rings. Regenerated cadaveric dermis by itself will not work. So instead, these guys used a donated trachea for its gross architecture and mechanical integrity, processed it in the same way that dermal matrices are processed to get rid of cells and immunogens, and then they seeded some host cells, then let it grow in situ. In actuality, the seeding step was largely irrelevant. When collagen-aminoglycan matrices (decellularized cadaveric materials) are implanted, circulating stem cells find them automatically. Pre-seeding could speed up the process by a week or so, but no big deal.

The cells which were seeded were NOT embryonic stem cells. They were just autogenous random marrow cells, some of which will be pluripotential, and able to regenerate tissues according to an embryonic model of tissue histogenesis. Note too that even if these were embryonic omnipotent stem cells, there is no such thing as a tracheal cell. What they implanted was a connective tissue matrix, generated by, and then repopulated by two and only two types of cells: fibroblasts and vascular cells. This is the supporting structure of all organs and tissues. Think of it like reinforced concrete. You can use cement and rebar to make a bridge, a road, a building, and so on, all with different shapes, loads, and functions, but it's all just cement and rebar.

Re:

That's a politically convinient way of looking at it. It ignores the fact that studies on ES cells advanced our understanding of adult stem cells, so the scores are irrevocably intertwined, but I can see why you'd like to ignore that fact.

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That's a politically convinient way of looking at it. It ignores the fact that studies on ES cells advanced our understanding of adult stem cells, so the scores are irrevocably intertwined, but I can see why you'd like to ignore that fact.

Good thing Bush allowed for federal funding for research on existing lines of embryonic stem cells.