Body’s Own Stem Cells Can Lead to Tooth Regeneration

From: http://cumc.columbia.edu/

Work at Columbia University College of Dental Medicine Holds Promise for a Biological Substitute for Dental Implants, According to Latest Journal of Dental Research

NEW YORK (May 19, 2010) - A technique pioneered in the Tissue Engineering and Regenerative Medicine Laboratory of Dr. Jeremy Mao, the Edward V. Zegarelli Professor of Dental Medicine at Columbia University Medical Center, can orchestrate stem cells to migrate to a three-dimensional scaffold infused with growth factor, holding the translational potential to yield an anatomically correct tooth in as soon as nine weeks once implanted.

People who have lost some or all of their adult teeth typically look to dentures, or, more recently, dental implants to improve a toothless appearance that can have a host of unsettling psycho-social ramifications. Despite being the preferred (but generally painful and potentially protracted) treatment for missing teeth nowadays, dental implants can fail and are unable to “remodel” with surrounding jaw bone that undergoes necessary changes throughout a person’s life.

Human molar scaffolding from the lab of Dr. Jeremy Mao

An animal-model study has shown that by homing stem cells to a scaffold made of natural materials and integrated in surrounding tissue, there is no need to use harvested stem cell lines, or create an environment outside of the body (e.g., a Petri dish) where the tooth is grown and then implanted once it has matured. The tooth instead can be grown “orthotopically,” or in the socket where the tooth will integrate with surrounding tissue in ways that are impossible with hard metals or other materials.

"These findings represent the first report of regeneration of anatomically shaped tooth-like structures in vivo, and by cell homing without cell delivery,” Dr. Mao and his colleagues say in the paper. "The potency of cell homing is substantiated not only by cell recruitment into scaffold microchannels, but also by the regeneration of periodontal ligaments and newly formed alveolar bone."

This study is published in the most recent Journal of Dental Research, the top-rated, peer-reviewed scientific journal dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry, the oral cavity and associated structures in health and disease.

Dental implants usually consist of a cone-shaped titanium screw with a roughened or smooth surface and are placed in the jaw bone. While implant surgery may be performed as an outpatient procedure, healing times vary widely and successful implantation is a result of multiple visits to different clinicians, including general dentists, oral surgeons, prosthodontists and periodontists. Implant patients must allow two to six months for healing and if the implant is installed too soon, it is possible that the implant may fail. The subsequent time to heal, graft and eventually put into place a new implant may take up to 18 months.

The work of Dr. Mao and his laboratory, however, holds manifold promise: a more natural process, faster recovery times and a harnessing of the body’s own potential to re-grow tissue that will not give out and could ultimately last the patient’s lifetime.

Jeremy Mao, D.D.S., Ph.D.

“A key consideration in tooth regeneration is finding a cost-effective approach that can translate into therapies for patients who cannot afford or who aren’t good candidates for dental implants,” Dr. Mao says. “Cell-homing-based tooth regeneration may provide a tangible pathway toward clinical translation.”

Dr. Ira B. Lamster, dean of the College of Dental Medicine, stated: “This research provides an example of what is achievable when today’s biology is applied to common clinical problems. Dr. Mao’s research is a look into the future of dental medicine.”

This research was supported by NIH ARRA Funding via 5RC2 DE020767 from the National Institute of Dental and Craniofacial Research. Columbia has filed patent applications relating to the engineered tooth and, through its technology transfer office, Columbia Technology Ventures, is actively seeking partners to help commercialize the technology.

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Man appears free of HIV after stem cell transplant

By Jacquelyne Froeber
From http://www.cnn.com/

A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.

The patient underwent a stem cell transplant and since, has not tested positive for HIV in his blood.

"The patient is fine," said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. "Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication."

The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man's leukemia, not the HIV itself.

However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.

While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.

"About a third of the people die [during such transplants], so it's just too much of a risk," Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient's immune system, leaving the patient vulnerable to infection, and then reintroduce a donor's stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.

Levy also said it's unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient's body to resurface at a later time, he said.

"This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can't spread, you never see it-- but it's there and it could do some damage," he said. "It's not the kind of approach that you could say, 'I've cured you.' I've eliminated the virus from your body." Health.com: 10 questions to ask a new partner before having sex

Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.

"There is no really conclusive explanation why we didn't observe any rebound of HIV," Hutter said. "This finding is very surprising."

Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.

Researchers including Hutter agree that the technique should not be used to treat HIV alone. "Some people may say, 'I want to do it,'" said Levy. A more logical -- and potentially safer -- approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.

Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. "It's definitely the wave of the future," he said. "As we continue to follow this one patient, we will learn a lot."

One drug that's currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs. Health.com: Who's most at risk for STDs?

In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person. Health.com:What should I do if the condom breaks?

"For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research," Hutter said.

Copyright Health Magazine 2009

Stem-cell injections could help heal fractures and treat bone diseases

By Fiona Macrae

Doctors may soon be able to patch up broken bones with a simple shot in the arm.

British scientists are testing injectable stem cells that can be guided around the body with a magnet.

Once they reach the diseased or damaged bone, they turn into new bone and cartilage.

Researcher Professor Alicia El Haj, of Keele University, said: 'The ultimate aim is to repair cartilage and bone.

The new technique could one day allow doctors to use a simple stem-cell injection to help treat broken limbs (posed by model)

'We have been able to grow new bone in mice. Now we will look at whether we can repair damaged sites in goats.

'We should be able to move to human trials within five years.'

The treatment centres on stem cells - 'blank' cells with the ability to turn into other cell types - drawn from a person's own bone marrow.

They are then coated with tiny magnetic particles before being injected into the body.

A magnet, in the form of a cuff or a bracelet, is used to guide them to where they are needed.

The magnetic field also provides the trigger needed for the stem cells to turn into bone and cartilage.

The treatment could be used to mend fractures as well as to provide an alternative to joint replacements for osteoarthritis patients.

Professor Al Haj said patients could be given stem cell jabs in their doctor's surgery, removing the need for expensive hospital stays.

She added: 'It's really cheap. It doesn't involve expensive drugs. Magnetic particles are really cheap. It's really exciting.'

Other British scientists have successfully used stem cells to treat patients with hip problems.

The Southampton University technique combines the person's own stem cells with donor bone cells to patch up damaged bones that would otherwise be held together with metal plates and pins.

Those treated include a man left in pain by a cyst that was eating away at his hip bone.
Researcher Richard Oreffo said: 'This was a patient who was in tremendous groin pain and was kept awake at night and this allowed us to alleviate those issues.'

Although just four patients have been treated so far, the operations are an important step in the quest for an off-the-peg treatment for fractures and bone disorders.

Professor Oreffo told the UK National Stem Cell Network's annual conference: 'The surgeon would like a simple product they could just lift out and drop into the patient.

'All of this is incremental but each is vital in allowing this to work.'

Professor Robert Nerem, of the Georgia Institute of Technology in the US, said stem cell science had much to offer medicine, both as a treatment and as a way of allowing scientists to test new drugs.

He said: 'In a sense we have a long way to go and yet the potential is just absolutely exciting.'

Breakthough stemcell surgery could end need for transplants

Heart disease patients in Britain could soon take part in a revolutionary stem cell surgery trial that could change the nature of heart surgery and ultimately end the need for transplants.

By Caroline Gammell

Heart disease affects more than a million people in the UK and kills around 120,000 people a year Photo: GETTY

It is believed that British patents could take the pioneering treatment, in which a patient's own cells are extracted and grown in a laboratory, in as little as a year.

Scientists have worked out a technique where human bone marrow cells are turned into human heart stem cells and then injected into the heart.

Laboratory grown heart stem cells were initially extensively tested on animals and trials on humans in Europe are due to start later this month.

Dr Jonathan Hill, a consultant cardiologist at London's King's College Hospital, is hoping to perform trials on British patients next year in conjunction with King's College London University.

"I have seen the results of the trials and they are very encouraging," he said. "We are negotiating to carry out human trials in the UK."

Professor Sian Harding, of Imperial College London, said being able to convert bone marrow stem cells into heart stem cell was a "big leap forward" in finding an "effective" treatment for heart failure.

"Placing heart stem cells into the heart to repair has a very good chance of working because the stem cells are the patient's own there are no problems with rejection," she said.

Prof Harding is working on turning embryo stem cells into heart stem cells but said her research was "still years away" from being used in patients.

Dr Duncan Dymond, a consultant cardiologist at London's Bart's Hospital, added: "Turning human stem cells into human heart cells is very exciting news.

"People with bad heart failure often lead a wretched life confined to home and unable to get out and about. If you are lucky you might get a heart transplant but many simply die before their time."

Last month, a method of cloning specialist versions of heart stem cells - known as "progenitor" cells - found in small quantities in human hearts received an international innovation award.

Last year, the Daily Telegraph disclosed how two heart attack patients in Britain had stem cells taken from bone marrow injected into their hearts in a bid to repair damaged tissue.

The most recent process was developed at the Mayo Clinic research centre in Minnesota.

As part of the planned human trials, 40 millilitres of bone marrow will be taken from a volunteer's hips.

The bone marrow is then grown in a laboratory into human heart stem cells using a special 'growth factor' protein.

The growth factor delivers a chemical signal to the stem cells to turn them from bone marrow cells into heart cells.

These cells are then infused into the patient's heart via a catheter in the groin and an improvement in a patient's condition is expected within a couple of weeks.

The development was disclosed during a major stem cell conference in New York and has been submitted to a leading medical journal.

Dr Christian Homsy of Cardio3 Biosciences - the company which is developing human heart stem cells - said: "Human heart stem cells repaired damaged areas of mice hearts in our trials. And we are convinced that we can do the same in humans.

"It is a very straightforward procedure and we would expect to see a patient's health to change quite rapidly over a period of several weeks to a couple of months. In the mouse trials it was quite quick but in humans we don't know yet."

Heart disease affects more than a million people in the UK and kills around 120,000 people a year.