Stem Cell Clinic

Researchers Use Light To Coax Stem Cells To Repair Teeth

By Stem Cell Medical Center

A Harvard-led team is the first to demonstrate the ability to use low-power light to trigger stem cells inside the body to regenerate tissue, an advance they reported in Science Translational Medicine. The research, led by Wyss Institute Core Faculty member David Mooney, Ph.D., lays the foundation for a host of clinical applications in restorative dentistry and regenerative medicine more broadly, such as wound healing, bone regeneration, and more.

The team used a low-power laser to trigger human dental stem cells to form dentin, the hard tissue that is similar to bone and makes up the bulk of teeth. What's more, they outlined the precise molecular mechanism involved, and demonstrated its prowess using multiple laboratory and animal models.

A number of biologically active molecules, such as regulatory proteins called growth factors, can trigger stem cells to differentiate into different cell types. Current regeneration efforts require scientists to isolate stem cells from the body, manipulate them in a laboratory, and return them to the bodyefforts that face a host of regulatory and technical hurdles to their clinical translation. But Mooney's approach is different and, he hopes, easier to get into the hands of practicing clinicians.

"Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low," said Mooney, who is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences (SEAS). "It would be a substantial advance in the field if we can regenerate teeth rather than replace them."

The team first turned to lead author and dentist Praveen Arany, D.D.S., Ph.D., who is now an Assistant Clinical Investigator at the National Institutes of Health (NIH). At the time of the research, he was a Harvard graduate student and then postdoctoral fellow affiliated with SEAS and the Wyss Institute.

Arany took rodents to the laboratory version of a dentist's office to drill holes in their molars, treat the tooth pulp that contains adult dental stem cells with low-dose laser treatments, applied temporary caps, and kept the animals comfortable and healthy. After about 12 weeks, high-resolution x-ray imaging and microscopy confirmed that the laser treatments triggered the enhanced dentin formation.

"It was definitely my first time doing rodent dentistry," said Arany, who faced several technical challenges in performing oral surgery on such a small scale. The dentin was strikingly similar in composition to normal dentin, but did have slightly different morphological organization. Moreover, the typical reparative dentin bridge seen in human teeth was not as readily apparent in the minute rodent teeth, owing to the technical challenges with the procedure.

"This is one of those rare cases where it would be easier to do this work on a human," Mooney said.

Next the team performed a series of culture-based experiments to unveil the precise molecular mechanism responsible for the regenerative effects of the laser treatment. It turns out that a ubiquitous regulatory cell protein called transforming growth factor beta-1 (TGF-1) played a pivotal role in triggering the dental stem cells to grow into dentin. TGF-1 exists in latent form until activated by any number of molecules.

Here is the chemical domino effect the team confirmed: In a dose-dependent manner, the laser first induced reactive oxygen species (ROS), which are chemically active molecules containing oxygen that play an important role in cellular function. The ROS activated the latent TGF-1complex which, in turn, differentiated the stem cells into dentin.

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Researchers Use Light To Coax Stem Cells To Repair Teeth

Study identifies cell-cycle phase that primes stem cells …

By Stem Cell Clinic

by Krista Conger

Resting, adult stem cells of many types of tissues enter a reversible "alert" phase in response to a distant injury, according to a study in mice by researchers at the Stanford University School of Medicine.

The study describes for the first time a new phase in the resting portion of the cell cycle. It also explains how stem cells prime themselves to rapidly respond to tissue damage without prematurely committing to energetically expensive (and possibly unnecessary) cell division. These alert cells are distinct from fully resting or fully activated stem cells, and they divide and repair subsequent tissue damage much more quickly than do fully resting stem cells.

The findings imply that nearly any type of injury may put stem cells throughout the body on notice for possible future regenerative needs.

"These alert stem cells changed markedly in response to a distant muscle injury," said Thomas Rando, MD, PhD, professor of neurobiology and neurological sciences. "They are partially awake and are poised to respond to additional challenges and make new tissue as needed. This is a systemic, or whole-body, response to injury that has never been seen before."

The researchers suggest the alert phase represents a novel form of cellular memory similar to that displayed by the immune system, which relies upon prior experiences to drive future responses.

Rando, who also directs Stanford's Glenn Laboratories for the Biology of Aging, is the senior author of the study, published online May 25 in Nature. Postdoctoral scholar Joseph Rodgers, PhD, is the lead author.

Resting state?

The researchers were studying the response of mouse muscle stem cells, or satellite cells, to muscle injury. Conventional wisdom holds that adult stem cells are by nature quiescenta term that indicates a profound resting state characterized by small size and no cell division. It's a kind of cellular deep freeze. In contrast, most other cells cycle through rounds of DNA replication and cell division in discrete, well-defined phases. A quiescent stem cell can "wake up" and enter the cell cycle in response to local signals of damage or other regeneration needs.

Rando and his colleagues were studying this activation process in laboratory mice by watching how muscle stem cells in one leg respond to a nearby muscle injury in the same leg. (Mice were anesthetized prior to a local injection of muscle-damaging toxin; they were given pain relief and antibiotics during the recovery period.) The researchers had planned to observe the quiescent muscle stem cells in the uninjured leg as a control for their experiment. However, they instead saw something unexpected.

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Forget the dentist's drill, use lasers to heal teeth

By Stem Cell Clinic

Open wide, this won't hurt a bit. That might actually be true if the dentist's drill is replaced by a promising low-powered laser that can prompt stem cells to make damaged hard tissue in teeth grow back. Such minimally invasive treatment could one day offer an easy way to repair or regrow our pearly whites.

When a tooth is chipped or damaged, dentists replace it with ceramic or some other inert material, but these deteriorate over time.

To find something better, researchers have begun to look to regenerative medicine and in particular to stem cells to promote tissue repair. Most potential stem cell therapies require the addition of growth factors or chemicals to coax dormant stem cells to differentiate into the required cell type. These chemicals would be applied either directly to the recipient's body, or to stem cells that have been removed from the body and cultured in a dish for implantation.

But such treatments have yet to make it into the doctor's clinic because the approach needs to be precisely controlled so that the stem cells don't differentiate uncontrollably.

Praveen Arany at the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, and his colleagues wondered whether they could use stem cells to heal teeth, but bypass the addition of chemicals by harnessing the body's existing mechanisms.

"Everything we need is in the existing tooth structure the adult stem cells, the growth factors, and exactly the right conditions," says Arany.

So they tried laser light, because it can promote regeneration in heart, skin, lung, and nerve tissues.

To mimic an injury, Arany's team used a drill to remove a piece of dentin the hard, calcified tissue beneath a tooth's enamel that doesn't normally regrow from the tooth of a rat. They then shone a non-ionising, low-power laser on the exposed tooth structure and the soft tissue underneath it. This allowed the light to reach the dental stem cells deep inside the pulp of the tooth.

Twelve weeks after a single 5-minute treatment, new dentin had formed in the cavity. Similar dentin production was seen in mice and in cultured human dental stem cells.

It not quite the end of the dentist's intervention though, they would still need to cap the tooth to protect it, because the stem cells that produce enamel are not present in adults.

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Forget the dentist's drill, use lasers to heal teeth

Mesoblast to accelerate operations in S'pore

By Uncategorized

SINGAPORE: Australia-based stem cell therapy firm Mesoblast has announced plans to accelerate commercial manufacturing operations in Singapore.

This is to prepare for new product launches in the United States and other major markets over the next couple of years.

Its existing operations in Singapore include making stem cell products for clinical trials under its contract with its partner, pharmaceutical company Lonza.

One of its key products still awaiting full approval is Prochymal, which Mesoblast says can help to more than double the survival rate of patients suffering from complications after receiving tissue transplants from donors -- known as graft versus host disease.

The global stem cell market is expected to grow at an average annual rate of 12 per cent between 2011 and 2016 to reach more than S$8 billion by 2016.

Mesoblast said commercial manufacturing requires a much larger capacity and operations must be scaled-up to meet regulatory demands.

Silviu Itescu, chief executive at Mesoblast, said: "We are now in a phase of making more investments in order to get our processes to commercial scale. That anticipates successful commercial launches.

"If we're successful in that over the next 18-24 months, then we're going to leverage the investment in our commercial facilities to be able to build up and prepare for launching of much larger opportunities in cardiovascular medicine, orthopaedics and diseases of immunity and inflammation which would require purpose-built facilities."

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Mesoblast to accelerate operations in S'pore

Catherine M. Bollard, MBCHB, MD, of Childrens National Performs Its First Treatment Using T-Cell Therapy On Child …

By Uncategorized

Washington, DC (PRWEB) May 28, 2014

Catherine M. Bollard, MBChB, MD, director of Childrens National Health Systems Program for Cell Enhancement and Technologies for Immunotherapy (CETI), and her team have performed the hospitals first treatment using T-cell therapy for a 6-month-old patient with congenital immune deficiency and a life-threatening virus infection.

Not only does this therapy offer a potentially curative treatment for patients who have failed conventional therapies for infections and cancer, the procedure sets the stage for avoiding potentially toxic drugs which can ultimately reduce inpatient stays and medical costs.

Its extremely important, offering a novel therapeutic thats not available at the majority of hospitals worldwide, said Dr. Bollard, a member of the Division of the Blood and Marrow Transplantation and senior scientist at Childrens Nationals Center for Cancer and Immunology Research at Childrens Research Institute. She is also the Principal Investigator and the Sheik Zayed Institute for Pediatric Surgical Innovation.

Childrens National is one of the few hospitals in the world to offer cellular therapy to treat life-threatening infections in patients with immune deficiencies as well as preventing or treating relapse in children with cancer. Cellular therapy uses the bodys own immune system to fight cancer and/or infections.

Patients from other hospitals and childrens facilities have been referred to Childrens National because of the uniqueness of the cell therapies we can now offer here, Dr. Bollard said. This kind of procedure reduces the amount of time for care and is not only cost effective for a hospital but also more tolerable for the patient, said Dr. Bollard. None of this could have been achieved without every one of those members within the CETI Program pulling together as a team to make it happen.

In the first of its kind cellular therapy achievement at Childrens National, Dr. Bollard and her team have shown that in the laboratory they can train nave or inexperienced immune system cells (T-cells) to kill cancer and/or viruses. In the first patient treated here, T-cells were grown from the patients mother and then injected into the young patient, who had severe combined immunodeficiency and a potentially life threatening virus infection. The T-cells the patient received (cytotoxic T lymphocytes) are a type of white blood cell that can kill virus-infected cells or cancer cells infected or cells that are damaged in other ways.

The babys immunodeficiency ailments included SCID, or severe combined immunodeficiency, a primary immune deficiency, which can result in the onset of one or more serious infections within the first months of life. Early in life, the child was infected with cytomegalovirus (CMV), a latent virus related to herpes that has significant morbidity and high mortality rates in immune compromised people. Initially, the patient had received a bone marrow transplant, but the CMV could not be cleared with the drug therapy he received after transplant, Dr. Bollard said.

Conventional treatment using antiviral agents is expensive and toxic and can be ineffective. Transfer of virus-specific T cytotoxic cells is seen as an alternative means of preventing and treating these infections. The hospital takes donor cells and manufactures them in the lab to fight specific viruses and/or cancer. The cells are given to the patients in the outpatient clinic, in a procedure that takes less than five minutes. The cytotoxic T-cells usually take within two to six weeks after which time the patient may no longer need other medications to treat or prevent infection.

We give these cells to the patient and then we hope that in a couple of weeks the CMV viral load falls to very low levels or even zero, Dr. Bollard said. This patient is 6 months old. By giving these T-cells, he can get off the drug therapy and spare his kidneys from the toxicity of the antiviral drugs.

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Orthocell to list on ASX

By Stem Cell Treatment

REGENERATIVE medicine firm Orthocell is seeking to raise $8 million to list on the Australian Securities Exchange (ASX).

Orthocell develops treatments for tendon, cartilage and soft tissue injuries, using a patient's own stem cells to repair the damage.

It is also developing a collagen-based product called CelGro, which provides mechanical strength to facilitate tissue repair.

"Musculoskeletal conditions are the most common reason to access health care services and costs Australia more than $4 billion each year," Orthocell chief executive Paul Anderson said in a statement on Thursday.

"Regenerative medicine aims to address these conditions by repairing and regenerating damaged tissue using the body's own building blocks in a more effective manner than ever before."

The company is offering 20 million shares at 40 cents per share.

The funds will be used to complete the development of CelGro and lodge it for regulatory approval in Australia.

Money will also go towards maintaining the regulatory approvals for the Ortho-ATI and Ortho-ACI stem cell treatments in Australia.

Orthocell will also use some for the funds to prepare for regulatory approval of Ortho-ATI in its first international market, which is likely to be either Europe or Japan.

The company says it has treated more than 400 patients, using the stem-cell treatments and is generating revenue from the treatments in Australia.

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Orthocell to list on ASX

Scientists Stimulate Dental Stem Cells With Laser

By Stem Cell Treatment

May 29, 2014

Brett Smith for redOrbit.com Your Universe Online

Researchers led by a team from Harvard University have successfully used a low-power laser to stimulate stem cell differentiation within the body, according to a study published on Wednesday by Science Translational Medicine.

[ Watch the Video: What Are Stem Cells? ]

The study team used a laser to stimulate dental stem cells and cause them to form dentin the hard tissue that makes up the majority of a tooth. The study was also able to identify and describe the molecular mechanism behind the growth process.

Study author David Mooney noted that the work could eventually lead to testing of a non-invasive dental procedure.

Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low, said Mooney, a professor of bioengineering at Harvards School of Engineering and Applied Sciences (SEAS), in a recent statement. It would be a substantial advance in the field if we can regenerate teeth rather than replace them.

The study team began by drilling holes in the molars of rodents. Next, the team treated the tooth pulp containing dental stem cells with a low-power laser, applied short term caps, and kept the animals secure and in good health. After around 12 weeks, observations confirmed that the treatment regimen induced improved dentin development.

It was definitely my first time doing rodent dentistry, said study author Dr. Praveen Arany, a clinical investigator at the National Institutes of Health. The dentin was strikingly similar in composition to normal dentin, but did have slightly different morphological organization.

Moreover, the typical reparative dentin bridge seen in human teeth was not as readily apparent in the minute rodent teeth, owing to the technical challenges with the procedure, he added.

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Scientists Stimulate Dental Stem Cells With Laser

Human stem cell treatment gets mice with MS-like condition walking again

By Stem Cell Treatment

Disabled mice regained the ability to walk less than two weeks after receiving human neural stem cells (Photo: Shutterstock)

When scientists at the University of Utah injected human stem cells into mice disabled by a condition similar to multiple sclerosis, they expected the cells to be rejected by the animals' bodies. It turned out that the cells were indeed rejected, but not before they got the mice walking again. The unexpected finding could have major implications for human MS sufferers.

In multiple sclerosis, the body's immune system attacks the myelin sheath that covers and insulates nerve fibers in the spinal cord, brain and optic nerve. With that insulation gone, the nerves short-circuit and malfunction, often compromising the patient's ability to walk among other things.

In the U Utah study (which was begun at the University of California, Irvine) human neural stem cells were grown in a Petri dish, then injected into the afflicted mice. The cells were grown under less crowded conditions than is usual, which reportedly resulted in their being "extremely potent."

As early as one week after being injected, there was no sign of the cells in the animals' bodies evidence that they had been rejected, as was assumed would happen. Within 10 to 14 days, however, the mice were walking and running. After six months, they still hadn't regressed.

This was reportedly due to the fact that the stem cells emitted chemical signals that instructed the rodents' own cells to repair the damaged myelin. Stem cells grown under the same conditions have since been shown to produce similar results, in tests performed by different laboratories.

Additional mouse trials are now planned to assess the safety and durability of the treatment, with hopes for human clinical trials down the road. "We want to try to move as quickly and carefully as possible," said Dr. Tom Lane, who led the study along with Dr. Jeanne Loring from the Center for Regenerative Medicine at The Scripps Research Institute. "I would love to see something that could promote repair and ease the burden that patients with MS have."

A paper on the research was recently published in the journal Stem Cell Reports.

Source: University of Utah

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Spinal cord, HIV stem cell treatments funded

By Stem Cell Treatment

Phil Reyes, one of the Parkinson's patients in Summit 4 Stem Cell, urges California's stem cell agency to support its research.

A potentially groundbreaking trial to treat spinal cord injuries with tissue grown from human embryonic stem cells will resume, after being funded by the California's stem cell agency.

The California Institute for Regenerative Medicine's governing committee approved without opposition a $14.3 million award to Asterias Biotherapeutics of Menlo Park. Asterias is taking over from Geron, which stopped clinical trials in November, 2011. Geron, also of Menlo Park, said it discontinued the trials for business reasons. Asterias is a subsidiary of Alameda-based BioTime.

Patients will be given transplants of neural tissue grown from the embryonic stem cells. The hope is that the cells will repair the severed connections, restoring movement and sensation below the injury site.

CIRM also unanimously approved a $5.6 million grant for another potential breakthrough: a clinical trial by Sangamo Biosciences of Richmond, Calif, to cure HIV infection with gene therapy. The trial is now in Phase II. Immune cells are taken from the patient and given a mutant form of a gene that HIV uses to get inside the cells. The mutated gene resists infection. The genetically altered cells are then given back to the patient.

Approval of both grants had been expected, as staff reports had recommended their approval. The agency met in San Diego.

In addition CIRM's Independent Citizens Oversight Committee funded $16.2 million in grants to bring three stem cell researchers to California. That vote was more contentious, with some committee members arguing that it made no sense to bring more scientists to California without a specific need. In addition, they argued that CIRM's main emphasis needs to be on funding clinical trials.

Member Jeff Sheehy said that bringing the scientists to California doesn't create more scientific capacity. However, a vote to deny funding failed, and a subsequent vote to approve funding passed.

CIRM is projected to run out of its $3 billion in bond funding by 2017, and supporters of the public agency are considering asking California voters for more money.

Also appearing at the CIRM meeting were advocates of funding a stem cell-based therapy for Parkinson's disease. The therapy, which may be approved in 2015 for a clinical trial, uses artificial embryonic stem cells called induced pluripotent stem cells grown from the patient's own skin cells. The group, Summit 4 Stem Cell, plans to ask for funding to help with the trial in the near future.

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Spinal cord, HIV stem cell treatments funded

Beverly Hills Orthopedic Institute Now Offering Stem Cell Procedures for Shoulder Injuries to Help Patients Achieve …

By Stem Cell Medicine

Beverly Hills, California (PRWEB) May 28, 2014

The Beverly Hills Orthopedic Institute is now offering stem cell procedures for patients with shoulder injuries to help achieve pain relief and avoid surgery. For individuals with rotator cuff tears, shoulder dislocations and tendonitis, the injections may heal the condition and get patients back into desired activities. For more information and scheduling, call (310) 247-0466.

When a person sustains a shoulder injury traumatically such as a rotator cuff tear or a shoulder dislocation, chronic pain may result ending up in a need for surgery. Surgery is often successful, however, there are significant risks and a potential lengthy recovery period.

As a Double Board Certified Los Angeles orthopedic surgeon, Dr. Raj has been a pioneer in stem cell procedures for shoulder injuries along with degenerative arthritis. He said, "Regenerative medicine procedures for shoulder injuries have been revolutionary. If you look at what happened to a professional dancer like Mark Ballas recently on Dancing With the Stars where he dislocated his shoulder, stem cell therapy can help stabilize the joint."

The stem cell procedures are performed as an outpatient and involve one of two methods. The first involves bone marrow derived stem cells, which are harvested directly from the patient, immediately processed, and then injected into the shoulder. The therapy contains concentrated stem cells and growth factors.

The second therapy option involves amniotic derived stem cells, which contain no embryonic stem cells and therefore avoid any ethical concerns. The amniotic fluid is processed at an FDA regulated lab, causes no rejection issues and is rich with stem cells, growth factors and hyaluronic acid.

Said Dr. Raj, "The combination of stem cells, growth factors, hyaluronic acid and cytokines in the fluid has been amazing for healing shoulder injuries. We've been able to help a lot of patients avoid the need for surgery and get back to high level athletic activities much sooner than with a surgery and associated rehab!"

Beverly Hills Orthopedic Institute accepts most insurance plans. Dr. Raj is an ABC News Medical Correspondent and a WebMD medical expert. For more information about the stem cell therapy and to make appointments, call (310) 247-0466.

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