Stem Cell Clinic

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?

Stem Cell Transplant Shows "Landmark" Promise for Treatment of Degenerative Disc Disease: Mayo Clinic

By Stem Cell Treatment

PHOENIX, March 7, 2014 /PRNewswire-USNewswire/ -- 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

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SOURCE American Academy of Pain Medicine

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Stem Cell Transplant Shows "Landmark" Promise for Treatment of Degenerative Disc Disease: Mayo Clinic

Controversial Stem Cell Company Moves Treatment out of U.S.

By Stem Cell Treatment

Celltex Therapeutics of Houston ceased treatment patients in the U.S. last year after a warning from regulators, and will now send patients for treatments to Mexico

Flickr/GE Healthcare

US citizens who had pinned their hopes on a company being able to offer stem-cell treatments close to home will now need to travel a little farther. Celltex Therapeutics of Houston, Texas, stopped treating patients in the United States last year following a warning from regulators. A 25 January e-mail to Celltex customers indicates that the firm will now follow in the footsteps of many other companies offering unproven stem-cell therapies and send its patients abroad for treatment but only to Mexico.

The stem-cell treatments offered by Celltex involved extracting adult stem cells from a patient, culturing them and then reinjecting them in a bid to replenish damaged tissue. It had been offering the treatment for more than a year with one of its high-profile customers being Texas governor, Rick Perry when the US Food and Drug Administration (FDA) wrote to the company on 24 September 2012 advising it that the stem cells it harvested and grew were more than minimally manipulated during Celltex's procedures. As such, the FDA regarded the cells as drugs, which would require the agency's approval to be used in treatments. The FDA also warned that Celltex had failed to address problems in its cell processing that inspectors from the agency had identified in an April 2012 inspection of its cell bank in Sugar Land, Texas. Shortly after it received the letter, Celltex stopped injecting stem cells into patients.

For customers who still had cells banked at Celltex and were wondering how to get them out, things became more chaotic when Celltex and RNL Bio, a company based in Seoul, South Korea, which operated the processing center and bank in Sugar Land, sued each other over financial disagreements. Celltex had to issue a restraining order just to gain access to the cells.

The January e-mail from Celltex reassures customers that their cells are safely stored in a facility in Houston and adds: We anticipate that we will be able to offer our stem cell therapy services to physicians in Mexico starting very soon! The e-mail also says that the company is building a new laboratory in Houston, to be opened in March.

Celltex adds that it will carry out an FDA-approved clinical trial, to start shortly after a March meeting with the FDA, pending a positive review from the regulator. However, the company had said in a 25 October e-mail to patients that it would start such a trial within two months and that patient enrolment could begin in late November.

Leigh Turner, a bioethicist at the University of Minnesota in Minneapolis, says that the move to Mexico is "not surprising", given the companys difficulties in the United States.

As Celltex's stem culturing and banking technology was licensed from RNL Bio, it is also not clear whether it has the expertise needed to launch a clinical trial on its own, says Turner. "It would have to build a stem-cell company from the ground floor up. I wouldnt say it is anywhere near the starting line."

Celltex did not respond to questions about how it would ship stem cells to Mexico or how it would perform the clinical research needed to seek FDA approval.

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Controversial Stem Cell Company Moves Treatment out of U.S.

Alzheimer's research team employs stem cells to understand disease processes and study new treatment

By Stem Cell Treatment

PUBLIC RELEASE DATE:

6-Mar-2014

Contact: Jessica Maki jmaki3@partners.org 617-525-6373 Brigham and Women's Hospital

Boston, MA A team of Alzheimer's disease (AD) researchers at Brigham and Women's Hospital (BWH) has been able to study the underlying causes of AD and develop assays to test newer approaches to treatment by using stem cells derived from related family members with a genetic predisposition to (AD).

"In the past, research of human cells impacted by AD has been largely limited to postmortem tissue samples from patients who have already succumbed to the disease," said Dr. Tracy L. Young-Pearse, corresponding author of the study recently published in Human Molecular Genetics and an investigator in the Center for Neurologic Diseases at BWH. "In this study, we were able to generate stem cells from skin biopsies of living family members who carry a mutation associated with early-onset AD. We guided these stem cells to become brain cells, where we could then investigate mechanisms of the disease process and test the effects of newer antibody treatments for AD."

The skin biopsies for the study were provided by a 57-year-old father with AD and his 33 year-old- daughter, who is currently asymptomatic for AD. Both harbor the "London" familial AD Amyloid Precursor Protein (APP) mutation, V7171. More than 200 different mutations are associated with familial AD. Depending on the mutation, carriers can begin exhibiting symptoms as early as their 30s and 40s. APPV7171 was the first mutation linked to familial AD and is the most common APP mutation.

The BWH researchers submitted the skin biopsies to the Harvard Stem Cell Institute, where the cells were converted into induced pluripotent stem cells (or iPSCs). Dr. Young-Pearse's lab then directed the stem cells derived from these samples into neurons specifically related to a particular region of the brain which is responsible for memory and cognitive function. The scientists studying these neurons made several important discoveries. First, they showed that the APPV7171 mutation alters APP subcellular location, amyloid-beta protein generation, and then alters Tau protein expression and phosphorylation which impacts the Tau protein's function and activity. Next, the researchers tested multiple amyloid-beta antibodies on the affected neurons. Here, they demonstrated that the secondary increase in Tau can be rescued by treatment with the amyloid -protein antibodies, providing direct evidence linking disease-relevant changes in amyloid-beta to aberrant Tau metabolism in living cells obtained directly from an AD patient.

While AD is characterized by the presence of amyloid-beta protein plaques and Tau protein tangles, observing living cell behavior and understanding the mechanisms and relationship between these abnormal protein deposits and tangles has been challenging. Experimental treatments for AD are using antibodies to try to neutralize the toxic effects of amyloid-beta, because they can bind to and clear the amyoid-beta peptide from the brain.

This study is the first of its kind to examine the effects of antibody therapy on human neurons derived directly from patients with familial AD.

"Amyloid-beta immunotherapy is a promising therapeutic option in AD, if delivered early in the disease process," said Dr. Young-Pearse. "Our study suggests that this stem cell model from actual patients may be useful in testing and comparing amyloid-beta antibodies, as well as other emerging therapeutic strategies in treating AD."

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Alzheimer's research team employs stem cells to understand disease processes and study new treatment

Patient-Specific Human Embryonic Stem Cells Created by Cloning

By Stem Cell Medicine

The breakthrough might set up another showdown about cloning for therapeutic purposes

OHSU Photos

From Nature magazine

It was hailed some 15 years ago as the great hope for a biomedical revolution: the use of cloning techniques to create perfectly matched tissues that would someday cure ailments ranging from diabetes to Parkinsons disease. Since then, the approach has been enveloped in ethical debate, tainted by fraud and, in recent years, overshadowed by a competing technology. Most groups gave up long ago on the finicky core method production of patient-specific embryonic stem cells (ESCs) from cloning. A quieter debate followed: do we still need therapeutic cloning?

A paper published this week by Shoukhrat Mitalipov, a reproductive biology specialist at the Oregon Health and Science University in Beaverton, and his colleagues is sure to rekindle that debate. Mitalipov and his team have finally created patient-specific ESCs through cloning, and they are keen to prove that the technology is worth pursuing.

Therapeutic cloning, or somatic-cell nuclear transfer (SCNT), begins with the same process used to create Dolly, the famous cloned sheep, in 1996. A donor cell from a body tissue such as skin is fused with an unfertilized egg from which the nucleus has been removed. The egg reprograms the DNA in the donor cell to an embryonic state and divides until it has reached the early, blastocyst stage. The cells are then harvested and cultured to create a stable cell line that is genetically matched to the donor and that can become almost any cell type in the human body.

Many scientists have tried to create human SCNT cell lines; none had succeeded until now. Most infamously, Woo Suk Hwang of Seoul National University in South Korea used hundreds of human eggs to report two successes, in 2004 and 2005. Both turned out to be fabricated. Other researchers made some headway. Mitalipov created SCNT lines in monkeys in 2007. And Dieter Egli, a regenerative medicine specialist at the New York Stem Cell Foundation, successfully produced human SCNT lines, but only when the eggs nucleus was left in the cell. As a result, the cells had abnormal numbers of chromosomes, limiting their use.

Monkeying around Mitalipov and his group began work on their new study last September, using eggs from young donors recruited through a university advertising campaign. In December, after some false starts, cells from four cloned embryos that Mitalipov had engineered began to grow. It looks like colonies, it looks like colonies, he kept thinking. Masahito Tachibana, a fertility specialist from Sendai, Japan, who is finishing a 5-year stint in Mitalipovs laboratory, nervously sectioned the 1-millimetre-wide clumps of cells and transferred them to new culture plates, where they continued to grow evidence of success. Mitalipov cancelled his holiday plans. I was happy to spend Christmas culturing cells, he says. My family understood.

The success came through minor technical tweaks. The researchers used inactivated Sendai virus (known to induce fusion of cells) to unite the egg and body cells, and an electric jolt to activate embryo development. When their first attempts produced six blastocysts but no stable cell lines, they added caffeine, which protects the egg from premature activation.

None of these techniques is new, but the researchers tested them in various combinations in more than 1,000 monkey eggs before moving on to human cells. They made the right improvements to the protocol, says Egli. Its big news. Its convincing. I believe it.

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