A research team is on the verge of a revolutionary breakthrough in stem cell research (updated)

MSD · Jan 2, 2013

I've been sitting on this one for a while. I'm not under any NDA or any binding contract. I was at a conference where Dr. Vacanti presented the research mentioned below along with a large amount of evidence that he has done what he claims to have done. He asked me to delete everything he presented that day and I did. I consider it a gentleman's agreement, and Dr. Vacanti was the commensurate gentleman, in speaking and working with me at this conference. As such, I reserve the right to remove this thread from public view if it turns out to be a problem. I have very limited notes on his presentation (I should mention that I have no formal education in biology past introductory courses,) but what I saw presented was mind-blowing, to say the least. The scientific research is currently in peer review.

With this article published, I feel comfortable sharing what I know with The TFP. Here is the article I'm referring to.

Anesthesiology News - Tissue-Engineering Anesthesiologist Redefines Stem Cells

When Charles Vacanti, MD, asks the question, one had better listen to the answer. After all, Dr. Vacanti, chair of anesthesiology, perioperative and pain medicine at Brigham and Women’s Hospital, in Boston, is a pioneer in tissue engineering and a leading expert in the field of stem cell research. But his response might come as a surprise: “I think not. I don’t think they naturally reside in tissue.”

That’s not to say that stem cells cannot be generated. Indeed, Dr. Vacanti has come to believe that stem cells, which are thought to have the ability to become virtually any line of cell in the body, often are the byproduct of the methods researchers have been using to isolate them. Quite literally, they can be shaken, stirred or chemically coaxed out of a dish.

Previously, scientists have believed that stem cells either reside in the tissues or can be induced by genetic manipulation, dedifferentiating them and allowing them in effect to become blank slates.

But in new, unpublished work, Dr. Vacanti’s group exposed various cell types to different forms of chemical and physical stresses—nearly killing them but performing no genetic manipulations, he said. Using a spectrographic analysis and green fluorescent imaging techniques, they observed that the stress caused the cells to exhibit genetic activity normally associated with embryonic stem cells.

“None of the [cells] before treatment expressed these embryonic stem cell markers,” said Dr. Vacanti, who presented some of the new findings at the 2012 annual meeting of the Society of Cardiovascular Anesthesiologists (SCA). “After treatment, they all did. After we injure any mature cell, it can be altered to become virtually identical” to the embryonic state in terms of gene expression (Figure 1).

The researchers then showed that, through stress-induced injuries, they could cause lymphocytes to become all three major cell lines: endoderm, mesoderm and ectoderm.

“Mature cells reverted back to stem cells and expressed all three germ layers,” Dr. Vacanti said.

Dr. Vacanti’s group has submitted their results for publication, and their manuscript is currently under review. But they have not discussed their findings publicly—indeed, Dr. Vacanti nearly had to scuttle his talk at SCA because his institution’s lawyers were filing patents on some aspects of the work up until the last minute. As a result, Anesthesiology News could not speak with independent experts about the new research.

Dr. Vacanti is no stranger to controversy. In 1995, he helped create what came to be known as the “ear mouse,” a lab rodent that served as a four-legged platform for growing human cartilage in the shape of an ear (Figure 2). Photos of the distorted animal sparked outrage in the animal rights community.

Although the notion that stem cells might be created without gene tinkering doubtless will come as a shock to many researchers, Dr. Vacanti said the cells are no less useful. “They have virtually unlimited potential for tissue repair,” he said.

In other work, Dr. Vacanti’s lab has demonstrated that the injury-induced stem cells can be used to regenerate everything from new tracheas to nerves in the spinal cord.

With the trachea, for example, the researchers procure normal mature adult cells, injure with chemicals the adult cells to generate stem cells that are grown in an incubator and then transfer to a scaffold. Once the scaffold is sufficiently populated with the correct cells, the researchers implant it into the affected area.

Lifesaving Gamble

In a test of the procedure that—for reasons that had nothing to do with the transplant itself—did not succeed, Dr. Vacanti’s group grew a trachea in the abdomen of a 14-year-old girl with a benign but aggressive airway tumor. Even after several surgeries and consultations at five institutions, he said, the mass kept returning, each time claiming more tracheal tissue.

“It looked like it was so large that when you took it out you could not pull the two ends of the trachea together and she would die,” he said. “She was told it was inoperable. Take her home, take her to Disney World, she’ll be dead in one year.”

With nothing to lose, Dr. Vacanti’s group suggested growing a tissue-engineered tracheal autograft using their technique. “We started to grow it in the incubator on cartilage from a rib biopsy. We seeded it onto a scaffold, and, after time, transplanted the scaffold into her abdomen, wrapped in her own omentum to have a vascularized pedicle,” Dr. Vacanti explained.

Once the new trachea was ready, the girl was prepped for the procedure. But after excising the tumor, the girl’s surgeons realized that she in fact had enough viable trachea left to remove the mass and repair the trachea without requiring the new organ.

In a sense, Dr. Vacanti said, although the graft was not needed, the fact that it existed as an option enabled the successful surgery. “If we had not grown it, they would not have operated and found it to be correctable,” he said.

Dr. Vacanti is submitting a proposal to the FDA to perform 10 such tracheal transplants in humans.

His group has conducted experiments using a similar procedure to repair the damaged spinal cords of animals. To date, they have performed the procedure on six monkeys, including two control animals and four that received stem cell injections. Of the four animals given the cells, two have experienced “virtually perfect” recoveries, Dr. Vacanti said, including the ability to run normally on a treadmill. The other two are still weak but have regained what he called “pretty good function.”

The studies so far have been conducted outside the United States, although Dr. Vacanti said he tried for several years to find a U.S. institution that would house the work. “No one was comfortable with resecting spinal cords because they felt that it burned a bridge irreversibly,” he said in an interview with Anesthesiology News. “Ultimately, you may not need to resect the cord. You need only resect the scar tissue” that forms at the site of the injury.

In fact, that seems to be the reason that stem cells therapies have failed to repair damage to the spinal cord. The new cells grow new spinal cord tissue, but not as fast as the fibrous tissue and scarring that forms at the site of the injury.

Dr. Vacanti said he hoped to be able to launch human trials of acute spinal cord injury, possibly as early as late 2015. He also would like to use the untreated control animals as a model for chronic spinal cord injury to see if the technique can rescue long-damaged nerves.

As for adverse effects, he said, “We have done thousands of these procedures and have not seen any evidence of malignancies.” Dr. Vacanti’s brother, Martin Vacanti, MD, a pathologist, has been analyzing the tissues for signs of abnormal cell growth. “He has been looking for chromosomal anomalies, among other things, and has found none.”
Click to expand...

What I saw presented was "simple" at its core.

-Adult cells were treated to co-express GFP (Gene Fluorescence Protein) with OCT4, a stem cell marker gene..
-These cells did not express GPF and therefore were not expressing OCT4.
-Cells were exposed to "chemical and physical stimuli" (I'm sure the patents and journal publications will specify exactly what was done.) No gene manipulation or gene insertion was involved. I don't remember his exact words, but to paraphrase: he always thought this was possible, and now he believes he has evidence.
-CD45 expression ceased in treated cells.
-Stem cell genes were activated.
-GFP was expressed (there were a bunch of graphs to show this, I'm sure they will be published with the paper on this.

Once the audience was hanging on his every word, he dropped the big reveal:

(Mouse) cells reverted to this embryonic-like state were implanted in prepared (mouse) uteri, and produced viable embryos at the E9.5 stage (9 and a half days of gestation); Apparently, 6 days of embryonic development is a threshold that's difficult to pass.

I realize that this will have a very limited audience, but It's a huge development in bio-technology and I'm enthusiastic to hear that it's in peer-review. (even though I don't know which journal.) The biggest consequence of this is that it will sidestep the ethical issue that conservative and pro-life individuals have with embryonic stem cell research. I'm sure that the idea that these induced pluripotent cells can produce viable embryos will raise the same red flags for some, but I suspect that the vast majority will acquiesce to it ... at least until some unscrupulous groups take it farther than intended and attempt to use it for human cloning.

Craven Morehead · Jan 2, 2013

Most of the details are way over my head except for the concept. I sure hope he is right. We're about due for a major medical breakthrough. This would be a good one.

Taliesin · Sep 5, 2013

Wow. Like Craven, it's mostly over my head.
But it does sound promising.

Can you post any future updates that you hear about?

Fremen · Sep 5, 2013

*thumbs-up, would gloss over again*

I just hope the politicians and religious nuts don't ruin any breakthroughs.

snowy · Sep 6, 2013

That is seriously amazing. This is huge. I can't wait to see where this research takes us.

MSD · Sep 8, 2013

For those who don't follow this sort of thing, a group of researchers in China have made a similar breakthrough.
Scientists develop safe and easy way to make stem cells

mixedmedia · Sep 8, 2013

That's pretty fascinating and exciting. We've been stuck at this roadblock for a long time.

And I'm pretty sure there will be plenty of religious nuts objecting to this based on the theory of 'playing god.'

GeneticShift · Sep 8, 2013

This is awesome. I've been following Dr. Vacanti and his work for a little while, and these articles are insane. I'm maintaining my slight skepticism, as I am supposed to, until I read the full article and see more reproducible results.

I really wish I could have been at that talk.

MSD · Feb 11, 2014

I'm a bit late updating the thread, but it's been published. PM me if you're interested in seeing the presentation I originally saw, it's available to the public for free, I just don't want to bombard them with referrals from TFP.
Acid bath offers easy path to stem cells : Nature News & Comment
The papers cited (PM me if you don't have access and really want to read them for yourself, I'll see what I can do.)
http://www.nature.com/nature/journal/v505/n7485/full/nature12968.html
http://www.nature.com/nature/journal/v505/n7485/full/nature12969.html

But wait, there's more! (spoiler: it works with human cells)
Extraordinary stem cell method tested in human tissue - health - 05 February 2014 - New Scientist

Talk about speedy work. Hot on the heels of the news that simply dipping adult mouse cells in acid could turn them into cells with the potential to turn into any cell in the body, it appears that the same thing may have been done using human cells.

The picture above, given to New Scientist by Charles Vacanti at Harvard Medical School, is said to be images of the first human "STAP cell" experiments.

Last week, the scientific world was bowled over by a study in Nature showing that an acidic environment turned adult mouse cells into "totipotent" stem cellsMovie Camera – which can turn into any cell in the body or placenta. The researchers called these new totipotent cells stimulus-triggered acquisition of pluripotency (STAP) cells.

"If they can do this in human cells, it changes everything," Rob Lanza of Advanced Cell Technologies in Marlborough, Massachusetts, said at the time. The technique promises cheaper, quicker and potentially more flexible cells for regenerative medicine, cancer therapy and cloning.

Now, Vacanti and his colleagues say they have taken human fibroblast cells and tested several environmental stressors on them in an attempt to recreate human STAP cells. He won't reveal what type of stressors were applied but he says the resulting cells appears similar in form to the mouse STAP cells. His team is in the process of testing to see just how stem-cell-like these cells are.

Vacanti says that the human cells took about a week to resemble STAP cells, and formed spherical clusters just like their mouse counterparts. Using a similar experimental set-up with green monkey (Chlorocebus sabaeus) cells, Vacanti says the resulting cells are behaving slightly differently. He says that may be due to the fact that the researchers used slightly different techniques. Both Vacanti and his Harvard colleague Koji Kojima emphasise that these results are only preliminary and much further analysis and validation is required.

"Even if these are STAP cells they may not necessarily have the same potential as mouse ones – they may not have the totipotency – which is one of the most interesting features of the mouse cells," says Sally Cowley, head of the James Martin Stem Cell Facility at the University of Oxford.

Pluripotent cells, such as embryonic stem cells, can form any cell in an embryo but not a placenta. Totipotent cells, however, can form any cell in an embryo and a placenta – meaning they have the potential to create life. The only cells known to be naturally totipotent are in embryos that have only undergone the first couple of cell divisions immediately after fertilisation.

Research using totipotent cells would have to be under very strict regulatory surveillance, says Cowley. "It would actually be ideal if the human cells could be pluripotent and not totipotent – it would make everyone's life a lot easier."

"However, the whole idea that adult cells are so plastic is incredibly fascinating," she says. "Using stem cells has been technically incredibly challenging up to now and if this is feasible in human cells it would make working with them cheaper, faster and technically a lot more feasible."
Click to expand...

Give it a year or two for submittal, peer review, and replication, but as far as I'm concerned, the debate over embryonic stem cells is over; we're about to see a shitstorm reignite over cloning.

PonyPotato · Feb 12, 2014

It does sound very interesting - I'm curious about whether human cells revert to stem cells naturally at all (within the body) when exposed to extreme stresses. It sounds like a great way for the body to respond and repair in times of stress.

It would be awesome if this concept could apply to the central nervous system. As of right now, most CNS damage becomes irreparable because of scarring. If stem cells could not only prevent scarring but assist in healing, and cells could be induced to change into them locally.. wow. This could be really awesome stuff!

MSD · Feb 12, 2014

Funny you should mention that ...
NSFW for surgical gore, but here's a screenshot of one of his slides showing a section of a lab rat's spine surgically removed
http://i.imgur.com/2HnKCQz.png

There was a post-treatment/recovery video of the rat walking on a treadmill as if it was completely unaware that it should have been paralyzed for life.

PonyPotato · Feb 13, 2014

MSD said: ↑

Funny you should mention that ...
NSFW for surgical gore, but here's a screenshot of one of his slides showing a section of a lab rat's spine surgically removed
http://i.imgur.com/2HnKCQz.png

There was a post-treatment/recovery video of the rat walking on a treadmill as if it was completely unaware that it should have been paralyzed for life.
Click to expand...

A rat walking on a treadmill doesn't necessarily mean that the spinal cord recovered fully - there are central pattern generators in the lower section of the spinal cord that controls the rear legs and they can have a stepping response in response to muscle stretch, not with any message from the brain or higher portions of the spinal cord.

Here's a video of a decerebrate cat (transected spinal cord) exhibiting gait on a treadmill:
View: http://www.youtube.com/watch?v=wPiLLplofYw

MSD · Feb 13, 2014

I sent you a link to the presentation I saw, like I said it's available online but I don't want to hammer them with referrer links from TFP. There's more than just the stem cell thing, you can see view the whole conference in addition to Vacanti's presentation.
If anyone wants to see it, send me a PM (Xenforo calls it "Start a conversation") and I'll give you the link.

MSD · Feb 18, 2014

Things are starting to look bad for the outcome of the study.
Acid-bath stem-cell study under investigation : Nature News & Comment

rogue49 · Feb 22, 2014

Yeah, the problem is when others start trying to duplicate your efforts.
Much less the conservative and political nature of many health boards and agencies.

I hope they are able to turn things around.

Shit, the things you have to do to get stuff approved.
I worked briefly at firms that specialized getting drugs and techniques through the FDA. (back in La Jolla and San Diego)
The amount of studies, investigation and research is profound.

Then again, I understand it too...because the damage to people could be significant.
Much less any ethics politics.

OtherSyde · Mar 9, 2014

I love science. BTW, when the HELL are they going to get this RISUG thing available? I SO want.

genuinemommy · Mar 12, 2014

This came out...
BBC News - Stem cells: Scientist asks for research to be withdrawn
Intense scrutiny over the work... and plagiarism in her PhD thesis. Not ok.

hamsterball · Mar 12, 2014

genuinemommy said: ↑

This came out...
BBC News - Stem cells: Scientist asks for research to be withdrawn
Intense scrutiny over the work... and plagiarism in her PhD thesis. Not ok.
Click to expand...

They always run into that little issue of peers reproducing the work, don't they?

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