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Stem cell study opens door to undiscovered world of biology

By Stem Cell Medical Center

13 hours ago This photo shows Dr. Sean Morrison, Director of the Children's Research Institute and senior author of the study, right, and Dr. Robert A.J. Signer, a postdoctoral research fellow and the study's first author. Credit: University of Texas Southwestern Medical Center

For the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells something scientists have long struggled to accomplish. The groundbreaking findings from the Children's Medical Center Research Institute at UT Southwestern (CRI) also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.

The discovery, published online today in Nature, measures protein production, a process known as translation, and shows that protein synthesis is not only fundamental to how stem cells are regulated, but also is critical to their regenerative potential.

"We unveiled new areas of cellular biology that no one has seen before," said Dr. Sean Morrison, Director of the Children's Research Institute, Professor of Pediatrics, and the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center. "No one has ever studied protein synthesis in somatic stem cells. This finding not only tells us something new about stem cell regulation, but opens up the ability to study differences in protein synthesis between many kinds of cells in the body. We believe there is an undiscovered world of biology that allows different kinds of cells to synthesize protein at different rates and in different ways, and that those differences are important for cellular survival."

Dr. Adrian Salic's laboratory at Harvard Medical School chemically modified the antibiotic puromycin in a way that made it possible to visualize and quantify the amount of protein synthesized by individual cells within the body. Dr. Robert A.J. Signer, a postdoctoral research fellow in Dr. Morrison's laboratory and first author of the study, realized that this reagent could be adapted to measure new protein synthesis by stem cells and other cells in the blood-forming system.

What they came across was astonishing, Dr. Morrison said. The findings suggested that different types of blood cells produce vastly different amounts of protein per hour, and stem cells in particular synthesize much less protein than any other blood-forming cells.

"This result suggests that blood-forming stem cells require a lower rate of protein synthesis as compared to other blood-forming cells," said Dr. Morrison, the paper's senior author.

Researchers applied the findings to a mouse model with a genetic mutation in a component of the ribosome the machinery that makes proteins and the rate of protein production was reduced in stem cells by 30 percent. The scientists also increased the rate of protein synthesis by deleting the tumor suppressor gene Pten in blood-forming stem cells. In both instances, stem cell function was noticeably impaired.

Together, these observations demonstrate that blood-forming stem cells require a highly regulated rate of protein synthesis, such that increases or decreases in that rate impair stem cell function.

"Amazingly, when the ribosomal mutant mice and the Pten mutant mice were bred together, stem cell function returned to normal, and we greatly delayed, and in some instances entirely blocked, the development of leukemia," Dr. Morrison said. "All of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right."

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Stem cell study opens door to undiscovered world of biology

Stem cell transplant shows 'landmark' promise for treatment of degenerative disc disease

By Stem Cell Treatment

Stem cell transplant was viable and effective in halting or reversing degenerative disc disease of the spine, a meta-analysis of animal studies showed, in a development expected to open up research in humans. Recent developments in stem cell research have made it possible to assess its effect on intervertebral disc (IVD) height, Mayo Clinic researchers reported in a scientific poster today at the 30th Annual Meeting of the American Academy of Pain Medicine.

"This landmark study draws the conclusion in pre-clinical animal studies that stem cell therapy for disc degenerative disease might be a potentially effective treatment for the very common condition that affects people's quality of life and productivity," said the senior author, Wenchun Qu, MD, PhD, of the Mayo Clinic in Rochester, Minn.

Dr. Qu said not only did disc height increase, but stem cell transplant also increased disc water content and improved appropriate gene expression. "These exciting developments place us in a position to prepare for translation of stem cell therapy for degenerative disc disease into clinical trials," he said.

The increase in disc height was due to restoration in the transplant group of the nucleus pulposus structure, which refers to the jelly-like substance in the disc, and an increased amount of water content, which is critical for the appropriate function of the disc as a cushion for the spinal column, the researchers concluded.

The researchers performed a literature search of MEDLINE, EMBASE and PsycINFO databases and also manually searched reference lists for original, randomized, controlled trials on animals that examined the association between IVD stem cell transplant and the change of disc height. Six studies met inclusion criteria. Differences between the studies necessitated the use of random-effects models to pool estimates of effect.

What they found was an over 23.6% increase in the disc height index in the transplant group compared with the placebo group (95% confidence interval [CI], 19.7-23.5; p<0.001). None of the 6 studies showed a decrease of the disc height index in the transplant group. Increases in the disc height index were statistically significant in all individual studies.

The authors commented that it is time to turn attention to the much-needed work of determining the safety, feasibility, efficacy of IVD stem cell transplant for humans.

"A hallmark of IVD degenerative disease is its poor self-repair capacity secondary to the loss of IVD cells. However, current available treatments fail to address the loss of cells and cellular functions. In fact, many invasive treatments further damage the disc, causing further degeneration in the diseased level or adjacent levels," said the lead study author Jason Dauffenbach, DO. "The goal of tissue engineering using stem cells is to restore the normal function and motion of the diseased human spine."

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The above story is based on materials provided by American Academy of Pain Medicine (AAPM). Note: Materials may be edited for content and length.

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Stem cell transplant shows 'landmark' promise for treatment of degenerative disc disease

Chicago Hospital Evaluates New Stem-Cell Therapy For Pain

By Stem Cell Doctors

CBS Chicago (con't)

Affordable Care Act Updates: CBSChicago.com/ACA

Health News & Information: CBSChicago.com/Health

(CBS) Is it the future of pain relief, the end of pain pills, physical therapy and knee or hip replacements?

CBS 2s Mary Kay Kleist looks at a new procedure offered at only a handful of places. Its still a bit controversial. But some doctors and their patients swear by it.

Linda Morning-Starpoole suffered terrible knee pain, the result of sports injuries when she was younger.

Traditional treatment might involve steroid injections, physical therapy and joint replacement. But she wanted an alternative.

The thought of me healing me with through my own stem cells is what sold me on the procedure, she says.

Heres how it works: Doctors take bone marrow from the hip and spin it in a machine to get the stem cells. Those cellsare then mixed with the patients platelets, a type of blood cell involved in healing.

The mixture is injected back into the joint, where the stem cells turn into new tissue, reduce pain and improve function.

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Chicago Hospital Evaluates New Stem-Cell Therapy For Pain

Bendable Needles Developed to Deliver Stem Cells into Brains

By Stem Cell Doctors

The flexible needles could help doctors deliver stem cells to broader areas of the brain with fewer injections. Such therapies are being investigated for Parkinson's disease, stroke and other neurodegenerative disorders

Flickr/TschiAe

As the surgical team prepared its instruments, a severed human head lay on the plastic tray, its face covered by a blue cloth. It had thawed over the past 24 hours, and a pinky-sized burr hole had been cut near the top of its skull. Scalp covered with salt-and-pepper stubble wrinkled above and below a pink strip of smooth bone.

Over the next two hours, the head would be scanned in a magnetic resonance imaging (MRI) machine as the researchers, led by Daniel Lim, a neurosurgeon and stem-cell scientist at the University of California, San Francisco, tested a flexible needle for delivering cells to the brain.

Several laboratories are investigating ways to treat neurological diseases by injecting cells into patients brains, and clinical trials are being conducted for Parkinsons disease, stroke and other neurodegenerative diseases. These studies follow experiments showing dramatic improvements in rats and mice. But as work on potentially therapeutic cells has surged ahead, necessary surgical techniques have lagged behind, says Lim.

In 2008 researchers led by Steven Goldman at the University of Rochester in New York showed that they could make severely disabled mice able to walk by injecting human glial progenitor cells into five sites in the rodents' brains.

Those results are encouraging, but a human brain is more than 1,000 times larger than a mouse brain, and delivering cells to the right places is much harder. People know how to get cells into animals but forget about the scale-up problem with humans, Lim says.

Necessary tools Working with bioengineers and neurosurgeons, Lim designed a needle that bends. First, a straight, thin tube is injected into the brain and a flexible nylon catheter pushed through it. A deflector inside the tube arcs the catheter up and away from the entry track, and an even narrower plunger ejects cells from the catheter. In one injection, the device can deposit cells anywhere within a 2-centimetre radius along the track, a volume bigger than an entire mouse brain.

Several researchers hope to use Lims device for clinical trials in brain cancer and neurodegenerative disease. Xianmin Zeng, a stem-cell scientist at the Buck Institute in Novato, California, who worked with Lim to test the device on swine, says she hopes to file an application to use the device in clinical trials for Parkinson's before the end of 2014.

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Bendable Needles Developed to Deliver Stem Cells into Brains

Guidelines on use of stem cell therapy

By Stem Cell Medicine

Google stem cell therapy and a whole host of results show up. Stem cell therapy for hair loss, diabetes, cancer and practically everything else. It is touted as the medicine of hope, the panacea for all ills.

But to ensure that this potentially-powerful technology is not misused in the country, the Indian Council of Medical Research has come up with a set of guidelines to regulate their use.

Under the new guidelines, any use of stem cells in patients will be considered research, not therapy.

This means stem cells can now only be used on patients within the purview of an approved, and monitored clinical trial anything outside of this would be considered malpractice. Ananthram Shetty, professor of minimally-invasive surgery at Canterbury Christ Church University, UK, said the guidelines are much-needed, welcome move in the right direction.

Prof. Shetty, who has been working with stem-cell technology for 27 years, and is often in India to demonstrate their use in research surgeries, said this would prevent anybody and everybody from claiming unproven benefits. Lots of people dont really understand what stem cells are. And those who have a terminal illness are willing to try anything. There are some people who use this to raise false hopes. And this is what the guidelines seek to stop, he said.

J.S. Rajkumar, chairman, Lifeline Hospital, however, said the guidelines could have been clearer about the use of adult stem cells over embryonic stem cells, he said. Now, the procedures involved and the time it would take could dissuade many, he said, while there is a real need for funds to be pumped in for research into this technology.

Another International Ear Care Day passed by on March 3.

It spelled out a clear message ear care can avoid hearing loss.

But the question is how many people know how to take care of their ears. What is interesting is the ear is a self-cleaning organ and does not require any kind of cleaning. But many clean their ears using safety pins, hair pins and even matchsticks.

While doctors advise against the use of such objects, they discourage the use of cotton buds too. Some heat coconut oil and pour into the ears. This could cause fungal infections. The ear drum is very thin and can be damaged, leading to loss of hearing, said M. Ramaniraj, professor of ENT, Government Stanley Medical College Hospital.

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Guidelines on use of stem cell therapy

Human Embryonic Stem Cells Restore Gerbil Hearing

By Stem Cell Medicine

A new study offers proof that stem cells can reconnect the inner ear to the brain

Marcelo Rivolta, University of Sheffield

By Virginia Gewin of Nature magazine

More than 275 million people have moderate-to-profound hearing loss, and many of those cases are caused by a breach in the connection between the inner ear and the brain.

Researchers have now shown how to repair a key component of that connection the auditory nerve by using human embryonic stem cells to restore hearing in gerbils. "We have the proof of concept that we can use human embryonic stem cells to repair the damaged ear," says lead author Marcelo Rivolta, a stem-cell biologist at the University of Sheffield, UK, whose research appears in Nature today. "More work needs to be done, but now we know it's possible."

Stem cells have been differentiated into auditory nerve cells before, but this is the first time that transplanted cells have successfully restored hearing in animals. Some in the field say that it is a pivotal step that will undoubtedly spur more research. Research has been stymied by reviewers wanting evidence that stem cells can connect the inner ear to the central nervous system, says Richard Altschuler, a developmental biologist at the Kresge Hearing Research Institute at the University of Michigan in Ann Arbor.

Rivolta has spent the past decade developing ways to differentiate human embryonic stem cells into the two cell types that are essential for hearing: auditory neurons, and the inner-ear hair cells that translate sound into electrical signals.

He treated human embryonic stem cells with two types of fibroblast growth factor (FGF) FGF3 and FGF10 to produce two, visually distinct, groups of primordial sensory cell. Those that had characteristics similar to hair cells were dubbed otic epithelial progenitors (OEPs), and those that looked more like neurons were dubbed otic neural progenitors (ONPs).

His team then transplanted ONPs into the ears of gerbils that had been treated with ouabain, a chemical that damages auditory nerves, but not hair cells. Ten weeks after the procedure, some ofthe transplanted cells had grown projections that formed connections to the brain stem. Subsequent testing showed that many of the animals could hear much fainter sounds after transplantation, with an overall improvement in hearing of 46%.

Hear this Rivoltas findings along with a study published in July showing that gene therapy can restore hearing in deaf-born mice reinforce a spate of studies demonstrating that stem cells and gene therapy can restore sensory functions, including smell (see 'Gene therapy restores sense of smell to mice') and vision (see 'Regenerative medicine repairs mice from top to toe').

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Human Embryonic Stem Cells Restore Gerbil Hearing

Tonight at 10pm: Guntersville Man Beats Cancer Through Stem Cell Transplant

By Stem Cell Clinic

Posted on: 10:16 am, March 6, 2014, by Matt Kroschel, updated on: 10:27pm, March 6, 2014

HUNTSVILLE, Ala. (WHNT) Given a 50/50 chance of survival, Joseph Overton knew he was not got to stop fighting cancer. Seven months after receiving a stem cell transplant at Huntsville Hospital, the 78-year-old Guntersville man is now cancer free and counting his blessings.

Overton was diagnosed with B cell lymphoma, a very aggressive form of cancer that spreads quickly.

But the diagnosis, however grim was not going to stop Overton from fighting and he had a special weapon in his corner, Dr. Jeremy Hon at Huntsville Hospital and his well-trained stem cell transplant team.

You come to me when you want to fight cancer, you dont come to me if you are looking for a referral to Hospice, said Dr. Hon. You come to me to fight.

A stem cell transplant is not for every patient, but Overton was a perfect candidate due to his healthy lifestyle and his type of cancer. According to information from the Mayo Clinic, a stem cell transplant can be performed if high-dose chemotherapy is given in the treatment of blood disorders such as leukemia, lymphoma, multiple myeloma, or amyloidosis.

A stem cell transplant helps your body make enough healthy white blood cells, red blood cells or platelets, and reduce your risk of life-threatening infections, anemia and bleeding following high-dose chemotherapy.

At Huntsville Hospital, the procedure used to replenish your bodys supply of healthy blood-forming cells is known as a autologous peripheral blood stem cell transplantmeaning the stem cells transplanted use cells from your own body.

Huntsville Hospital is the only hospital in a 100-mile radius with the equipment and staff needed for a stem cell transplant. The hospital purchased new machinery for the department this past year.

Overton is back to doing what he loves thanks to the stem cell transplant. During the last year he took a trip to Disney, a cruise and has started building houses again.

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Tonight at 10pm: Guntersville Man Beats Cancer Through Stem Cell Transplant

In the Flesh: The Embedded Dangers of Untested Stem Cell Cosmetics

By Uncategorized

Unapproved procedures and skin care products endanger consumers and clinical research

Credit: Nissim Benvenisty, via Wikimedia Commons

When cosmetic surgeon Allan Wu first heard the woman's complaint, he wondered if she was imagining things or making it up. A resident of Los Angeles in her late sixties, she explained that she could not open her right eye without considerable pain and that every time she forced it open, she heard a strange clicka sharp sound, like a tiny castanet snapping shut. After examining her in person at The Morrow Institute in Rancho Mirage, Calif., Wu could see that something was wrong: Her eyelid drooped stubbornly, and the area around her eye was somewhat swollen. Six and a half hours of surgery later, he and his colleagues had dug out small chunks of bone from the woman's eyelid and tissue surrounding her eye, which was scratched but largely intact. The clicks she heard were the bone fragments grinding against one another.

About three months earlier the woman had opted for a relatively new kind of cosmetic procedure at a different clinic in Beverly Hillsa face-lift that made use of her own adult stem cells. First, cosmetic surgeons had removed some the woman's abdominal fat with liposuction and isolated the adult stem cells withina family of cells that can make many copies of themselves in an immature state and can develop into several different kinds of mature tissue. In this case the doctors extracted mesenchymal stem cellswhich can turn into bone, cartilage or fat, among other tissuesand injected those cells back into her face, especially around her eyes. The procedure cost her more than $20,000, Wu recollects. Such face-lifts supposedly rejuvenate the skin because stem cells turn into brand-new tissue and release chemicals that help heal aging cells and stimulate nearby cells to proliferate.

During the face-lift her clinicians had also injected some dermal filler, which plastic surgeons have safely used for more than 20 years to reduce the appearance of wrinkles. The principal component of such fillers is calcium hydroxylapatite, a mineral with which cell biologists encourage mesenchymal stem cells to turn into bonea fact that escaped the woman's clinicians. Wu thinks this unanticipated interaction explains her predicament. He successfully removed the pieces of bone from her eyelid in 2009 and says she is doing well today, but some living stem cells may linger in her face. These cells could turn into bone or other out-of-place tissues once again.

Dozens, perhaps hundreds, of clinics across the country offer a variety of similar, untested stem cell treatments for both cosmetic and medical purposes. Costing between $3,000 and $30,000, the treatments promise to alleviate everything from wrinkles to joint pain to autism. The U.S. Food and Drug Administration (FDA) has not approved any of these treatments and, with a limited budget, is struggling to keep track of all the unapproved therapies on the market. At the same time, pills, oils, creams and moisturizers that allegedly contain the right combination of ingredients to mobilize the body's resident stem cells, or contain chemicals extracted from the stem cells in plants and animals, are popping up in pharmacies and online. There's Stem Cell 100, for example, MEGA STEM and Apple Stem Cell Cloud Cream. Few of these cosmetics have been properly tested in published experiments, yet the companies that manufacture them say they may heal damaged organs, slow or reverse natural aging, restore youthful energy and revitalize the skin. Whether such cosmetics may also produce unintended and potentially harmful effects remains largely unexamined. The increasing number of untested and unauthorized stem cell treatments threaten both people who buy them and researchers hoping to conduct clinical trials for promising stem cell medicine.

When is a skin cream a drug? So far, the FDA has only approved one stem cell treatment: a transplant of bone marrow stem cells for people with the blood cancer leukemia. Among the increasing number of unapproved stem cell treatments, some clearly violate the FDA's regulations whereas others may technically be legal without its approval. In July 2012, for example, the U.S. District Court upheld an injunction brought by the FDA against Colorado-based Regenerative Sciences to regulate just one of the company's several stem cell treatments for various joint injuries as an "unapproved biological drug product." The decision hinged on what constitutes "minimal manipulation" of cells in the lab before they are injected into patients. In the treatment that the FDA won the right to regulate, stem cells are grown and modified in the lab for several weeks before they are returned to patients; in Regenerative Sciences's other treatments, patients' stem cells are extracted and injected within a day or two. Regenerative Sciences now offers the legally problematic treatment at a Cayman Island facility.

Many stem cell cosmetics reside in a legal gray area. Unlike drugs and "biologics" made from living cells and tissues, cosmetics do not require premarket approval from the FDA. But stem cell cosmetics often satisfy the FDA's definitions for both cosmetics and drugs. In September 2012 the FDA posted a letter on its Web site warning Lancme, a division of L'Oral, that the way it describes its Genifique skin care products qualify the creams and serums as unapproved drugs: they are supposed to "boost the activity of genes," for example, and "improve the condition of stem cells." Other times the difference between needing or not needing FDA approval comes down to linguistic nuancethe difference between claiming that a product does something or appears to do something.

Personal Cell Sciences, in Eatontown, N.J., sells some of the more sophisticated stem cellbased cosmetics: an eye cream, moisturizer and serum infused with chemicals derived from a consumer's own stem cells. According to its website and marketing materials, these products help "make skin more supple and radiant," "reduce the appearance of fine lines and wrinkles around the eyes and lips," "improve cellular renewal" and "stimulate cell turnover for renewed texture and tone." In exchange for $3,000, Personal Cell Sciences will arrange for a participating physician to vacuum about 60 cubic centimeters (one quarter cup) of a customer's fat from beneath his or her skin and ship it on ice to American CryoStem Corp. in Red Bank, N.J., where laboratory technicians isolate and grow the customer's mesenchymal stem cells to around 30 million strong. Half these cells are frozen for storage; from the other half, technicians harvest hundreds of different kinds of exuded growth factors and cytokinesmolecules that help heal damaged cells and encourage cells to divide, among other functions. These molecules are mixed with many other ingredientsincluding green tea extract, caffeine and vitaminsto create the company's various "U Autologous" skin care products, which are then sold back to the consumer for between $400 and $800. When the customer wants a refill, technicians thaw some of the frozen cells, collect more cytokines and produce new bottles of cream.

In an unpublished safety trial sponsored by Personal Cell Sciences, Frederic Stern of the Stern Center for Aesthetic Surgery in Bellevue, Wash., and his colleagues monitored 19 patients for eight weeks as they used the U Autologous products on the left sides of their faces. A computer program meant to objectively analyze photos of the volunteers' faces measured an average of 25.6 percent reduction in the volume of wrinkles on the treated side of the face. Analysis of tissue biopsies revealed increased levels of the protein elastin, which helps keep skin taut, and no signs of unusual or cancerous cell growth.

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In the Flesh: The Embedded Dangers of Untested Stem Cell Cosmetics

What's Next for Stem Cells and Regenerative Medicine?

By Uncategorized

See Inside Mar 19, 2013 |By Christine Gorman

Richard Clark, NIH

Researchers are now experimenting with stem cellsprogenitor cells that can develop into many different types of tissueto coax the bodies of a few individuals to heal themselves. Some of the most advanced clinical trials so far involve treating congestive heart disease and regrowing muscles in soldiers who were wounded in an explosion. But new developments are happening so quickly that investigators have come up with a new nameregenerative medicineto describe the emerging field.

Many of the stem cells being studied are referred to as pluripotent, meaning they can give rise to any of the cell types in the body but they cannot give rise on their own to an entirely new body. (Only the earliest embryonic cells, which occur just after fertilization, can give rise to a whole other organism by themselves.) Other stem cells, such as the ones found in the adult body, are multipotent, meaning they can develop into a limited number of different tissue types.

One of the most common stem cell treatments being studied is a procedure that extracts a few stem cells from a person's body and grows them in large quantities in the laboratorywhat scientists refer to as expanding the number of stem cells. Once a sufficient number have been produced in this manner, the investigators inject them back into the patient.

The bone marrow is a rich source of adult stem cells, containing both the hematopoietic stem cells that give rise to the various types of blood and the so-called mesenchymal cells, which can develop into bone, cartilage and fat. Mesenchymal cells are found in the bone marrow and various other places in the body, although whether all mesenchymal stem cells are truly interchangeable irrespective of origin is unclear.

Scientific American spoke with Mahendra Rao, director of the Center for Regenerative Medicine at the National Institutes of Health in Bethesda, Md., to get a sense of the sorts of new developments that might occur in regenerative medicine in the next five years or so.

[An edited transcript of the interview follows.]

Why is there so much excitement about regenerative medicine? You could say that medicine up until now has been all about replacements. If your heart valve isn't working, you replace it with another valve, say from a pig. With regenerative medicine, you're treating the cause and using your own cells to perform the replacement. The hope is that by regenerating the tissue, you're causing the repairs to grow so that it's like normal.

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What's Next for Stem Cells and Regenerative Medicine?

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