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Posts Tagged ‘regeneration’

The cells could be further studied for eventual application to human therapy

The findings are the first time pluripotent stem cells have been found in an adult animal, according to researchers at MIT and the Howard Hughes Medical Institute.

Pluripotent stem cells have a unique ability to turn into any kind of cell, which is what makes them so valuable for disease research, tissue regeneration and other fields. But these cells are only found in embryos, or are induced in complex lab processes. Adults have stem cells, but they have greater specificity — blood stem cells can turn into any constituent part of the blood, and skin stem cells can turn into skin or hair, but they can’t turn into other cells like neurons, for instance.

But flatworms, or more properly planarians, seemingly can create all their cells from a limited clump. If you cut off a chunk of it, it won’t die — you’ll soon wind up with two fully fledged, healthy planarians. Researchers wanted to know whether the animals’ regenerative properties were the work of one “all-purpose” stem cell, or groups of specific stem cells working together.

To figure this out, researchers led by Peter Reddien, Daniel Wagner and Irving Wang at MIT exposed the worms to ionizing radiation, robbing their cells of their ability to divide and regenerate. Without the ability to grow new cells, the animal would slowly die. The team killed off all the dividing cells except a rare group called cNeoblasts, and watched as those remaining cells divided to form large colonies of replacement cells.

Then they did something truly weird. Wang and Reddien harvested a single cNeoblast from one type of planarian. Then they gave a different kind of planarian, one that did not have its own neoblasts and couldn’t regenerate, a lethal dose of radiation. Its tissues started to die, from the head down toward its tail. Then they implanted the first worm’s neoblast into the tail of the second, dying worm.

They watched as the transplanted cNeoblast multiplied, differentiated and “ultimately replaced all the host’s tissues,” according to a news release from the Whitehead Institute for Biomedical Research. Descendants of the single neoblast cell differentiated into neuronal, intestinal and other adult cell types, taking over the jobs of the host’s dying cells. The newly restored worm was an exact genetic copy of the cNeoblast donor. All this from one single cell.

The results were published in today's issue of the journal Science.

In a news release, Wagner said planarians have already solved the problem of regeneration, and scientists want to determine how it works.

“One day, we'll examine what are the key differences between what's possible in this animal and what's possible in a mouse or a person,” he said.

Anthony Atala wows the crowd

“It’s like baking a cake,” Atala said.

A few years ago, Atala figured out how to produce human tissue with a desktop inkjet printer, using cells as the printer ink. In a TED talk last year, he described printing heart valves and other tissues. This week at TED, he brought one of his patients on stage. When he was 10, Luke Massella was among the first people to receive a re-engineered organ — he was born with spina bifida and received a new bladder grown from his own tissue. Now he’s a healthy college student.

The organ-printing process employs scanners that collect a 3-D image of the organ that needs to be replaced. A small tissue sample seeds the printer, which replicates the tissue layer by layer to build a new organ, all in about six or seven hours. It would use the patient’s own tissue, so it avoids any organ rejection issues.

During Atala's talk, a specially designed printer was about three hours into printing a kidney model built out of biocompatible materials. He also brought a completed model to show to the audience.

Initial reports suggested Atala had printed a working kidney, but it was actually a kidney-shaped mold with no internal structures or vasculature, according to Wake Forest University Baptist Medical Center, where Atala is a regenerative medicine specialist.

He said someday, scanners and printers could conceivably be used to treat wounds. A flatbed scanner could scan a patient’s wound, while a printer adds the right types of tissues to fill it back in. “You can print right on the patient,” Atala said, according to a report on the talk at Fast Company.

Atala also described using a patient's failed organ as a scaffold for a new version, filling it with new tissue. This could help address the challenge of building blood vessels, which remains one of the greatest challenges in tissue engineering.

Atala said about 90 percent of people on organ transplant lists are waiting for kidneys, but donors are few and far between. Meanwhile, patients must undergo painful and complicated dialysis treatment. And mechanical replacements are still a few years away. Atala said regenerative medicine could one day solve the organ shortage crisis, replacing failing body parts on demand. 


[via Independent Online]

Correction: An earlier version of this post cited coverage by the Agence France-Presse newswire, among other sources, which incorrectly reported that Massella had received a printed kidney 10 years ago and that Atala printed a functional kidney onstage. In fact, Massella received a re-engineered bladder, and Atala printed a dummy kidney mold to demonstrate how the technique could provide transplantable organs someday.

If a stem cell treatment replaced the most common cosmetic surgery procedure, it could pave the way for much wider medical use of the potent little cells

Experimenting with non-vital organs is safer and subject to a much more limited set of regulations, since the stakes in experimenting on a human heart are much higher than on less-crucial appendages. Additionally, FDA approval isn’t required to relocate cells that are removed and returned to the same person in one procedure. And breast augmentation is the most commonly performed plastic surgery in the U.S., earning almost $1 billion in 2009.

Human trials have demonstrated that adipose-derived stem cells can be successful treating a variety of bodily failures, improving aerobic capacity in people with heart disease, increasing blood supply and pumping capacity in heart attack survivors and decreasing incontinence in prostatectomy survivors by 89 percent. In rat studies, the cells improved kidney function.

Trials in breast growth (and re-growth in the case of breast cancer survivors recovering from mastectomies, lumpectomies and quadrantectomies) have been promising. Since the tissues induce the formation of blood vessels, the regenerative cells link the blood supply to the fat cells they’re traveling with, presenting a much lower risk of reabsorption than the injection of fat cells alone. In 2007, a cosmetic surgeon in Japan began a human study and reported that patients injected with the stem-cell-loaded fat solution grew an average of 4 centimeters in breast circumference while the tissue remained soft and natural.

If the San Diego-based biotech company Cytori Therapeutics that developed the centrifuge system gets FDA approval for clinical trials, they could find themselves at the forefront of the regenerative medical industry; but not before they tap in to the sizeable market of women willing to trade surplus fat elsewhere for a more shapely bustline.

The first study, conducted at the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco, reprogrammed fibroblasts -- structural heart cells that cannot beat -- into beating cells by adding a handful of genes into the mix. The team took the genes that turn cells in a developing embryo into cardiomyocytes, or beating heart tissue cells.

By adding these genes -- there were only three of them -- to fibroblasts removed from mice and reinserted the gene-loaded fibroblasts into living mice, the cells transformed into beating heart tissue within a day.

The second study looked to amphibians like newts to figure out why mammals cannot regenerate tissue like amphibians can. Some studies have theorized that over time, mammals gave up the ability to regenerate because the process can also lead to runaway cell division -- cancer. A genetic tumor suppressor may have evolved somewhere along the way that keeps humans from regenerating everything from severed limbs to damaged heart tissue.

Researchers found that a couple of genes -- retinoblastoma, or Rb, and another known as ARF -- are involved in tumor suppression. So they blocked the genes in mice with heart problems. Their heart cells then began to grow and divide, replacing old and damaged tissue.

Of course, both of these therapies need a whole lot of scrutiny, testing, and more testing before they end up in human trials, but either or both could spell big news for those living under the constant specter of heart failure. When humans suffer from heart attacks, their heart cells die (how many depends on the severity of the attack and how long they are deprived of oxygen). This leaves inactive scar tissue behind that does not regenerate, meaning that person is permanently left with a faulty heart that never heals (hence all the assistive mechanical devices like the one former VP Dick Cheney just received).

Something like 5 million Americans live with heart failure constantly threatening. The ability to regenerate those damaged cardiovascular tissues that keep our hearts strong would allow our bodies to repair themselves without resorting to extremely risky transplant surgeries or invasive implanted medical devices.

[Reuters]

For the first time, researchers have proven this can work, by stimulating the body's own stem cells to re-grow joint tissue around an implantable scaffold. In a study published this week in the journal Lancet, scientists report the technique successfully regenerated joints in living rabbits, even as the joints were being used.

Columbia University researchers, funded by the National Institutes of Health, removed forelimb thigh joints from 10 rabbits and made 3-D models of them. They added criss-crossed microchannels to serve as a scaffold, Technology Review reports.

They added a growth factor protein to the scaffolds and implanted them in the rabbits' forelegs, following the same surgical procedure used to implant titanium replacement joints. The growth protein drew the rabbits' own stem cells to the location of the missing joint, where they regenerated bone and cartilage.

Within four weeks, the rabbits were able to walk around normally, the researchers say.

The work simply proves the concept, and much more work needs to be done before this technique could be tried in humans, according to Columbia scientist Jeremy Mao, who led the research. Two-legged creatures place much more pressure on their leg joints, and people in need of joint replacement may have other medical issues that could affect joint regeneration.

Still, as Tech Review notes, the finding is promising. Re-growing cartilage and bone even while the joints are in use could mean a simpler and longer-lasting solution for joint replacement.

[Eurekalert, Technology Review]

According to a study published in the latest Journal of Dental Research, a new tissue regeneration technique may allow people to simply regrow a new set of pearly whites.

Dr. Jeremy Mao, the Edward V. Zegarelli Professor of Dental Medicine at Columbia University Medical Center, has unveiled a growth factor-infused, three-dimensional scaffold with the potential to regenerate an anatomically correct tooth in just nine weeks from implantation. By using a procedure developed in the university's Tissue Engineering and Regenerative Medicine Laboratory, Dr. Mao can direct the body's own stem cells toward the scaffold, which is made of natural materials. Once the stem cells have colonized the scaffold, a tooth can grow in the socket and then merge with the surrounding tissue.

Dr. Mao's technique not only eliminates the need to grow teeth in a Petri dish, but it is the first to achieve regeneration of anatomically correct teeth by using the body's own resources. Factor in the faster recovery time and the comparatively natural process of regrowth (as opposed to implantation), and you have a massively appealing dental treatment.

Columbia University has already filed patent applications in regard to the technology and is seeking associates to aid in its commercialization. In the meantime, Dr. Mao is considering the best approach for applying his technique to cost-effective clinical therapies.

[Columbia University Medical Center]

The device itself consists of a tank holding a mixture of harvested skin cells, stem cells, and nutrients, and a computer-controlled nozzle that places the cells exactly where they need to go. The spray works similar to a color printer, first spraying down a layer of fibroblast skin cells as a substrate, and then blasting on a layer of protective keratinocyte cells. Both sprays also contain a slurry of some undeveloped skin cells.

In initial tests on wounded lab mice, burns treated with the cell printer healed in two weeks, compared with the usual five weeks skin grafts take to heal. Additionally, the mice with the printed-on skin showed less scarring and more hair regeneration, as the sprayed-on stem cells better incorporated themselves into all the various cell types of the burned flesh.

Successful mouse tests have driven the Wake Forest scientists onward to tests with pigs, whose skin more closely resembles that of humans. After the tests with pigs conclude, the doctors can finally move on to human trials, and eventual FDA approval. Additionally, the Wake Forest team is working with the U.S. Armed Forces Institute of Regenerative Medicine to utilize this technology on the battlefield, to print shut bullet wounds and blast damage.

[Reuters]