Scientific dogma has long held that a single stem cell is responsible for all of the components of the blood system. Now in a paper published in the journal Cell Stem Cell, a group at Baylor College of Medicine is challenging that dogma. The group found that there were different, distinct adult stem cell subtypes that contribute to different components of the blood system. They verified the “stem cell nature” of these different subtypes by transplanting single stem cells into individual mice, and were able to confirm that these subtypes exist, can maintain a stable population of the stem cells over time, and behave as expected. Senior author Dr. Margaret Goodell said:

“From a scientific point of view, it’s making us re-evaluate the view of the stem cells that come from adults. It challenges the dogma that there is one type of stem cell.”

The study has significance for stem cell patient treatments as well. According to Goodell:

“People have been looking for purer and purer stem cell types. In doing that, they may not be getting all the stem cell types they need. Maybe in the clinic, it is better to have less pure types.”

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Growing lots of adult stem cells in the lab, for study or for a patient treatment, has been difficult in the past. While some groups have successfully grown large numbers of adult stem cells, many labs have difficulties keeping the cells growing for more than a few days. Now scientists at Weill Cornell have shown that culturing adult stem cells with endothelial cells, the cells that compose the innermost linings of blood vessels, is the key to growing unlimited amounts of adult stem cells. The research group reasoned that because endothelial cells line blood vessels and are often in contact with adult stem cells, these cells might play a significant role in the growth and maintenance of stem cells. Using a mouse model, the scientists were able to grow adult stem cells for weeks at a time and increase the number of cells over 400-fold. They also showed that even after one year, there was no indication of tumor formation from the adult stem cells. Senior author, Dr. Shahin Rafii, noted:

“This study will have a major impact on the treatment of any blood-related disorder that requires a stem cell transplant.”

Previous work from Dr. Rafii’s lab had demonstrated that endothelial cells are not “passive conduits”
for delivery of oxygen and nutrients but also produce novel stem-cell-active growth factors.

The breakthrough promises broad clinical benefits, from bone marrow transplantation to therapies for heart, brain, skin and lungs. If the system continues to be validated, physicians could use any source of hematopoietic (blood-forming) stem cells, grow large numbers, and bank the adult stem cells for transplantation into patients.

The paper is published in the journal Cell Stem Cell.

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Two new published studies provide further evidence for the effectiveness of adult stem cells in repairing heart damage, and suggest possible mechanisms for how the cells work.

A Brazil-Florida collaboration found that adult stem cells injected directly into the heart could relieve angina. The researchers used injection directly into the heart based on previous results showing higher uptake of cells administered in this way. All eight of the angina patients in the study benefitted. Lead author Dr. Nelson Americo Hossne, Jr. said:

“For our patients, angina symptom relief began as early as three months post-procedure with continuing improvement through the twelfth month and sustained improvement past 18 months. Symptom relief improved in all patients, suggesting that the effect is sustained, not transitory.”

The authors conclude that their results show the procedure to be safe and effective, and suggest neoangiogenesis, the stimulation of new blood vessel growth, as the main stem cell mechanism of action in these patients.

A separate published study by Chinese scientists suggests that a small protein called apelin, which affects the strength of muscle contraction, may play a role in adult stem cell repair of heart. Twenty patients experiencing severe heart failure were treated with their own bone marrow adult stem cells, while another twenty heart failure patients were treated with standard medications; both groups were compared against twenty healthy adults. All twenty of the heart failure patients treated with adult stem cells showed significant improvement in cardiac function within 21 days of treatment, while the standard medication patients showed no improvement. Interestingly, the adult stem cell-treated patients showed a large increase in levels of apelin, correlated with the improvement in cardiac function. They postulate that the secretion of apelin is induced by the grafted adult stem cells.

Both studies were published in the journal Cell Transplantation. Dr. Amit Patel of the University of Utah School of Medicine and an Editor of the journal said:

“Both studies demonstrate a possible mechanistic approach in a clinical trial either. These important findings further enhance the understanding of the use of bone marrow derived cell therapy for the treatment of cardiovascular disease.”

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An international team of scientists has used modified adult stem cells to repair the spinal cord in rats, restoring function. In spinal cord injury, the protective insulating sheath around the spinal cord is destroyed, a process called demyelination. Without the normal insulation, spinal cord nerves can’t send electrical impulses. The scientists isolated adult spinal cord stem cells, then modified them to produce the protein ciliary neurotrophic factor (CNTF), a growth factor that stimulates cell survival and nerve growth. The results, published in the Journal of Neuroscience, showed recovered signaling in spinal cords of the treated rats and enhanced recovery of hindlimb movement. The authors conclude that using modified adult stem cells can enhance remyelination and facilitate functional recovery after traumatic spinal cord injury. Patients have already been treated with similar nasal adult stem cells. The authors of this current study note that besides confirming previous results with adult stem cells, these results indicate that optimal recovery will include grafts with additional stimulation such as the added growth factor they used.

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UCLA scientists have shown that they can engineer adult blood stem cells so that they lack a molecule necessary for HIV infection. The CCR5 receptor is a protein molecule on the surface of cells that is bound by HIV when the virus infects certain immune cells, acting as a receptor for the virus. The scientists used “short hairpin RNA” to knock down the expression of the CCR5 molecule in the human adult stem cells, effectively preventing the protein from being produced. These cells could reconstitute the immune system in a mouse model, indicating that the function of the immune cells was not inhibited. But the human cells, now without the CCR5 protein receptor, resisted HIV infection. The study, published in the journal Blood, provides a potential method for controlling HIV infection in patients.

The study follows a previous report of successful adult stem cell treatment for leukemia that also appears to have controlled HIV infection in the patient. The doctors specifically used an adult stem cell donor whose cells lacked the CCR5 molecule.

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Compared to the questionable success of embryonic stem cells, adult stem cells have been achieving some real successes in retinal repair studies, without the complication issues of tumors, etc. and without the ethical problems associated with embryonic stem cells.

A couple of examples of recently published studies.

In a paper published February 15, 2010, Oregon scientists showed that they could use bone marrow-derived adult stem cells to treat a rat model of retinitis pigmentosa. Visual function was significantly preserved in this study. An added benefit was that the cells could be easily grown in culture and administered intravenously; once injected, they traveled to the retina where they exerted their protective effect. The study highlights the possibility of using a patient’s own adult stem cells for treatment of retinitis, diabetic retinopathy, and macular degeneration.

A study by Canadian and Japanese researchers used human retinal stem cells that had been modified to increase their differentiation potential. When injected into the eyes of mice, the adult stem cells survived and differentiated into photoreceptors. Injected into a mutant mouse strain that lacks functional photoreceptors, the adult stem cells significantly improved visual function. The study was published online in the journal Stem Cells December 11, 2009.

In Louisville, they are close to initiating a clinical trial using adult stem cells for treatment of macular degeneration.

Looking at a different part of the eye, adult stem cells have already been used successfully in patients to treat corneal blindness.

There are other examples of real adult stem cell successes for visual repair if we want to go back further. And unlike “potential” embryonic stem cell experiments which rely on sacrificing some human beings, adult stem cell research doesn’t require destroying the cell donor, instead often using the patient’s own adult stem cells for the treatment. Real success and real science.

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A news story out yesterday exemplifies the “successes” of embryonic stem cells. The story proclaimed that scientists had “successfully used mouse embryonic stem cells to replace diseased retinal cells and restore sight in a mouse model of retinitis pigmentosa.” Sounds pretty good? Later there is the requisite hyperbole about treatments, that “Once the complication issues are addressed” and a list of retinal diseases that will be treated with embryonic stem cells.

Wait a minute. Complication issues?

However, complications of benign tumors and retinal detachments were seen in some of the mice, so Dr. Tsang and colleagues will optimize techniques to decrease the incidence of these complications in human embryonic stem cells before testing in human patients can begin.

I would hope that they’d eliminate the complications first, not just decrease the incidence. And just how many of the mice are represented by “some”?

The abstract in the journal Transplantation gives a bit more detail:

Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes.

So, a quarter of the mice showed improvement, but more than half showed complications including tumors…

So much for an embryonic success.

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When she was 30, Jennifer Osman was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), a neurological disorder that attacks the peripheral nervous system, progressively weakening and numbing its victim. She began the usual treatment of immunosuppressant therapy. As the disease progressed, Jennifer was at the hospital three or four times a week. As things progressed, she became weaker and nearly paralyzed. Her husband Rick said that she had become so bad that she had no strength in her arms & legs, and he had to carry her to bed and sometimes even had to feed her. They were told that the disease could eventually attack the nerves supporting her lungs and stop her from breathing, killing her by the time she was 40.

Then Jennifer signed up for an adult stem cell study run by Dr. Richard Burt, chief of the Division of Immunotherapy at Northwestern University Feinberg School of Medicine. Her adult stem cells were collected and she received chemotherapy to knock out the rogue immune cells attacking her nervous system. Shortly after, on April 1, 2005, Jennifer received a transplant of her own adult stem cells and her immune system, now rebooted, began to rebuild itself. The process was slow and grueling, but she has taken no medication for the disease since 2008. Today, almost five years since her transplant, she is nearly symptom-free.

“This is my life, a healthy life. Back to normal.”

Rick points out:

“It’s really important to us that people know (about the stem cell procedure), because we found out about this from watching TV. If we hadn’t seen that broadcast, she probably wouldn’t be here today.”

The Osmans have a website to tell Jennifer’s story and communicate with other CIDP patients. Jennifer is looking forward to updating the site on April 1, five years to the day that she received her adult stem cell transplant.

You can see a video of Amy Daniels (another of Burt’s patients) and her story of treatment for scleroderma, as well as other patient stories, at Stem Cell Research Facts.

Dr. Burt has performed the first adult stem cell transplants in the country, and sometimes in the world, for patients with many autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, Crohn’s disease, systemic lupus erythematosus, Type I (juvenile) diabetes, and of course CIDP. Burt said Northwestern has done about 350 of these transplants so far. A number of his clinical trials are currently ongoing, including one for CIDP. Dr. Burt says:

“When I first came up with this idea … people said, ‘Why are you wasting your time?’ I ended up following my passion, and it’s been fabulous. The amazing thing is, traditional medicine has just kind of come to a stop with these patients. What we’ve done is we’ve changed that.”

According to Burt, the treatment has come a long way, as Medicare and several insurance companies will now cover it.

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Previous stories focused on the science of treating peripheral artery disease with adult stem cells. Often overlooked are the people whose lives have been changed or even saved by adult stem cell treatments.

Helen Thomas, 80, of Hastings, Michigan is one of those people. Helen’s painful circulatory problem in her leg meant she had trouble walking, rarely left home, and was facing amputation of her leg. But her physician, Kenneth Merriman of Hastings, asked around at a medical conference and found Dr. Randall Franz, who was doing a clinical trial at Grant Medical Center in Columbus, Ohio. Franz injected Helen’s own adult stem cells into her leg, causing new blood vessels to grow. Helen is now up and about, back to normal.

“It was a miracle. I’m walking, and I wouldn’t be walking without the stem cells. I have my leg. They saved my life. I told them they saved my life.”

Helen’s daughter Mary said:

“It’s just life-changing”

Initial patient results have been published in the Journal of Vascular Surgery.

HT: Andy McDonald

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Last Friday the National Institutes of Health announced that they were proposing a “technical change” in their Guidelines for destruction of human embryos, a.k.a. Guidelines for Human Embryonic Stem Cell Research.

The change would allow use of younger human embryos in experiments. As published today in the Federal Register, the change in definition for embryonic stem cells would be:

For the purpose of these Guidelines, “human embryonic stem cells (hESCs)” are cells that are derived from the inner cell mass of blastocyst stage human embryos pluripotent cells that are derived from early stage human embryos, up to and including the blastocyst stage, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.

You can submit comments on this proposed change. Note that the deadline for comments is 11:59pm EST on March 24, 2010 (a 30-day comment period.) Apparently NIH doesn’t want to read a lot of critiques–comments are limited to 6,000 characters, including spaces. It remains to be seen whether NIH will ignore the majority of comments as it did for the initial guidelines.

Continue reading »

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Researchers at the Medical College of Georgia are conducting the first FDA-approved adult stem cell clinical trial in cerebral palsy. The trial, led by Dr. James Carroll, professor and chief of pediatric neurology in MCG School of Medicine, will investigate whether stem cells from umbilical cord blood can improve the quality of life for children with cerebral palsy. Umbilical cord blood is rich in adult-type stem cells, which can divide and morph into different types of cells throughout the body and have already shown published success in treating numerous diseases and injuries in patients.

Dr. Joanne Kurtzberg at Duke has done preliminary clinical work in this area and notes that in about 100 children, intravenous administration of autologous (the person’s own) cord blood is safe and feasible. Her results are as yet unpublished, and she cautions that there are “some hints that there may be some benefits” but that “it’s very, very difficult to successfully assess efficacy.” Previous anecdotal reports have indicated benefits for treated children.

Benefits of cord blood stem cells vs. embryonic stem cells were recently reviewed by Harris in the British Journal of Haematology.

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Just in time for Valentine’s Day, scientists at Birmingham University’s Nanoscale Physics Research Lab have produced a picture of the world’s smallest Valentine heart–palladium atoms clustered together, only 8 nanometers wide. The palladium atoms spontaneously clustered together in this arrangement when placed on a special carbon base. The heart had to be viewed through a powerful electron microscope.

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Adult stem cells continue to show success after success at improving the health of patients, even though many still haven’t heard the good news. But while many physicians and scientists (and politicians) ignore the tangible benefits of adult stem cells, veterinarians have pushed ahead. The latest story is that of the over-$1-million-winning horse Thorn Song.

The horse had been severely injured in his final start at Del Mar last summer and had “an almost zero chance” at survival after developing laminitis. Laminitis is a disease of the hoof that is extremely painful and often fatal for horses; it is the disease that led to 2006 Kentucky Derby winner Barbaro being euthanized.

Dr. Doug Herthel is the vet who founded Alamo Pintado Equine Medical Center and treated Thorn Song. Alamo Pintado was the first private equine practice in the United States to open an onsite adult stem cell laboratory; they have used the procedure successfully to treat hundreds of horses with joint, tendon, and ligament injuries. However, only a few horses have been treated for laminitis with adult stem cells. According to Dr. Herthel:

“I thought there would still be a less than 10% chance for him even if we tried stem cell. But within 48 hours we saw a turnaround. There was a dramatic decrease in pain and swelling, and within two weeks we started seeing amazing hoof growth. We were blown away. It went beyond our expectations. It may be the most exciting thing I have ever seen. Technology is moving forward.”

Adult stem cells have successfully treated many horses and dogs. And thousands of human patients, too. And that’s not horsing around.

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Peripheral arterial disease (PAD) is a painful circulatory problem in the legs that affects 10 million Americans. If left untreated, it can lead to serious complications including stroke, amputation and death. Doctors at Grant Medical Center in Columbus, Ohio report that they have used the patient’s own adult stem cells to treat PAD. In their paper published in the Journal of Vascular Surgery, they report that 8 of 9 patients treated showed some improvement, and 6 of the 9 patients avoided any amputation. Dr. Randall W. Franz, lead author on the study, noted that:

“We were pleasantly surprised by our results. This is cutting-edge technology that could benefit millions of Americans with PAD.”

The six patients had restored blood flow that eliminated their constant pain and healed their ulcerations. Dr. Franz says that 16 patients have now received the procedure, with 13 patients avoiding major amputation.

The technique in this study used adult stem cells taken directly from the patients’ hips instead of sending the cells to a laboratory for culture, a process that can postpone injection for several weeks. Co-author Dr. Thomas Hankins said:

“This technique sheds new light on stem cell treatment and has the potential to become the gold-standard therapy for PAD.”

This new study on PAD follows another recent report on saving legs using the patient’s own adult stem cells to treat critical limb ischemia.

Adult stem cells are saving limbs and saving lives now.

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A new report published online in Nature describes how Stanford scientists turned mouse skin cells directly into nerve cells, without any intermediate stem cell step. Starting with mouse skin cells in the lab dish, they added three nerve-specific genes using viruses. According to senior author Marius Wernig, the “induced neuronal cells” are fully functional.

“We actively and directly induced one cell type to become a completely different cell type. These are fully functional neurons. They can do all the principal things that neurons in the brain do. That includes making connections with and signaling to other nerve cells.”

Wernig’s group took a page from Yamanaka’s book in discovering the right mix of factors to add. They started with 19 genes expressed in neural tissue, testing various 5-gene and 3-gene sets until finally narrowing down to just three genes that worked to convert the skin fibroblasts to neurons. The change took a week with an efficiency of almost 20 percent, faster and better than the reprogramming seen with iPS cells. Wernig said:

“We were very surprised by both the timing and the efficiency. This is much more straightforward than going through iPS cells, and it’s likely to be a very viable alternative. That means reprogramming doesn’t only go backward, but can occur in any direction. If you extrapolate from this, you could probably turn any cell in your body into any other cell if you just know the right factors.”

Wernig and his colleagues are now trying to do the same direct reprogramming with human cells and Stanford has applied for a patent on the process.

In 2008, Doug Melton’s team at Harvard used a similar technique to directly reprogram adult mouse pancreas cells, turning them into insulin-secreting beta cells. That cell reprogramming was accomplished within the bodies of the mice by infecting their pancreas with viruses containing three transcription factors; the newly-formed beta cells could ameliorate hypoglycemia in the mice. In his Nature paper, Melton noted that the new direct reprogramming method

“suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.”

Commenting on the latest Stanford results, Melton thought it was a major advance because it used cells that could be easily obtained from a person, and takes a more direct route to changing cells than Yamanaka’s iPS cell method, which creates undifferentiated embryonic-like stem cells.

“Instead of trying to turn them back into pluripotent stem cells and then make those into differentiated cells, he’s short- circuiting that process and saying let’s go right from one readily available cell to another cell of interest.”

Perhaps the most significant fact is that the cells make the change without first becoming a pluripotent type of stem cell, like an embryonic stem cell. Given that pluripotent stem cells are notoriously difficult to control, bypassing that step with direct reprogramming becomes an extremely attractive method to transform cells.

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Spanish scientists report use of adult stem cells to treat corneal blindness. The University Institute of Applied Oftal-molecular Biology in Valladolid, and the Institute of Genetic and Molecular Biology, report a positive result in 90% of patients who have undergone the new treatment. Patients receive transplants of adult stem cells to regenerate the cornea. The doctors note that as many as 88,000 people in Spain could benefit from this adult stem cell treatment. They also say that applying this technique for various types of blindness could reduce health care costs.

This news from Spain follows a similar report of restoring sight to patients in the U.K. with adult stem cells.

¡Células madre adultas son un gran avance de la medicina!
[Adult stem cells are a great advance for medicine!]

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Aerobic exercise such as running or jogging stimulates the growth of new brain cells and improves the memory and ability to learn. Scientists divided mice into two groups: one group was given a running wheel they could use at any time, and the other group was given a couch and TV with remote control had no exercise wheel. The study showed that even a few days of running stimulates the brain to grow new cells in a part of the brain involved in memory and recall, and the exercised mice performed better on memory and learning tests. The new study is published in the Proceedings of the National Academy of Sciences.

Previous studies have shown increased neural stem cell production can be induced by exercise, even in aged mice, and that new brain stem cells are important for memory and learning. Earlier work suggested that exercise stimulated neural stem cell formation in humans as well.

Another advantage of running is that you can generate some electricity.

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A number of different reports have shown that adult stem cells can save limbs that might otherwise have been amputated. The most recent results, published in Bone Marrow Transplantation, reported salvage of legs in seven out of nine patients treated with their own peripheral blood adult stem cells. The paper also gives a nice summary of some of the previous clinical trials in this area.

Critical limb ischemia, the severe loss of oxygen to extremities, is an end-stage of peripheral artery disease (PAD). often results in amputation of the affected limb, and can be life-threatening. Cathy Ballzigler almost lost her life, but after receiving her own adult stem cells, both her life and her leg were saved. Tom Fisher is another example; he was facing amputation of his leg due to diabetic complications, but the leg was saved after injection of his own adult stem cells.

A few of the clinical trials currently available.

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A new study shows that adult stem cells encased in a spongy matrix can be used to fill in large gaps in bones, providing a potential alternative to bone grafts. Georgia Tech researchers tested the method in rats with large bone gaps, to simulate massive injuries. Bone marrow-derived mesenchymal adult stem cells or amniotic fluid stem cells were tested. Eight weeks after the treatment, new bone bridged the gaps in four of nine defects treated with scaffolds seeded with adult stem cells, one of nine defects in the amniotic stem cell group, and none of the defects in rats treated with the scaffold alone.

According to lead author Robert Guldberg:

“Massive bone injuries are among the most challenging problems that orthopedic surgeons face, and they are commonly seen as a result of accidents as well as in soldiers returning from war. This study shows that there is promise in treating these injuries by delivering stem cells to the injury site. These are injuries that would not heal without significant medical intervention.”

The results, published in the Proceedings of the National Academy of Sciences, also indicated that adult stem cells are shy about being watched while they work. In an attempt to track the stem cells, some experiments used cells labeled with fluorescent quantum dots. In those experiments, the researchers found that the cells showed lower therapeutic benefit.

Previously researchers have had good success with smaller bone breaks in patients, even with non-healing injuries, using adult stem cells.

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Scientists in the Netherlands have created lab-grown pork. The Dutch labs in the In-vitro Meat Consortium, a network of publicly funded Dutch research institutions, have been fakin’ bacon since 2006. They admit that the texture isn’t quite right yet (currently the “meat” has the consistency and feel of scallop.) They start with pig muscle stem cells, growing the cells in a nutrient medium (here’s one generic example) in the lab. They estimate it would take about 30 days to make a small pork chop.

So far their main problem is protein content–protein makes up about 99% of normal meat, but only about 80% in their lab-grown meat, which gives it a soggy, flimsy consistency. Prof. Mark Post at Eindhoven University said:

“What we have at the moment is rather like wasted muscle tissue. We need to find ways of improving it by training it and stretching it, but we will get there.”

Apparently none of the researchers have actually eaten the lab-made meat yet either, and Prof. Post said the lower protein content means it probably wouldn’t taste anything like pork. For now, they hope to grow large quantities of the cells in huge bioreactors to make processed meats like minced meat, hamburgers or hot dogs. They also envision incorporating other cell types and molecules, such as omega 3 fatty acids from fish.

A recent Nature Biotechnology article noted that several groups were concentrating on production of lab-grown meat, primarily with a view toward the potential environmental benefits, with the possibility that “by 2022 consumers could be tucking into ‘VatBeef’ grown in a lab.” PETA is also sponsoring a competition for the first success at lab-grown chicken. Supposedly the packages will be marked “incubator range” rather than free-range.

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