New NUH study to test stem cells as treatment for liver disease – TODAYonline

SINGAPORE The use of stem cell treatment to repair liver cirrhosis, or hardening of the liver, will be tested in a clinical trial here involving 46 patients and costing S$2.6 million.

The four-year study, which was launched yesterday, came amid a growing waiting list in Singapore for a liver transplant, which is currently the only cure for patients with end-stage liver cirrhosis.

Conducted by a multi-centre team from several restructured hospitals here, the study is led by the National University Hospital (NUH).

Liver failure is one of the top 20 causes of death in Singapore, but many patients are not suitable for a transplant due to factors such as age and surgical fitness.

Out of every five patients doctors see with end-stage liver disease, only one qualifies for a liver transplant, said Dr Dan Yock Young, principal investigator of the clinical trial and senior consultant at NUHs division of gastroenterology and hepatology.

(A liver transplant) is curative, but it is a complex procedure, and many patients are not suitable for it. For these patients, treatment is limited, but morbidity and mortality rates are high as high as 50 per cent in one year and this is probably worse than many (of the) other terminal illnesses we talk about today, he said.

Animal studies conducted over the last five years have shown that stem cells can reconstruct the micro-environment of a normal liver.

Like how branches are of critical importance in supporting the leaves and fruits of a tree, the endothelial (stem) cells contribute to supporting a nutritious environment for the hepatocyte (liver) cells, Dr Dan explained.

While similar stem-cell studies have been conducted in other centres in Asia, there has been no definitive evidence of the benefits of the treatment for liver patients.

The study will recruit 46 patients aged between 40 and 70 years old, and who are at the terminal stages of chronic liver disease, over three years. It is funded by the National Medical Research Council.

During the clinical trial, patients will be divided into a therapeutic group and a control group.

All patients will receive an injection to stimulate their bone marrow cells as part of the supportive treatment for their liver cirrhosis. However, only patients in the study group will have the stem cells from the bone marrow extracted and deposited directly into their liver for more targeted repair.

Using ones own stem cells will avoid the problem of cell rejection.

The liver tissue will be examined three months later, and an investigation to compare pre- and post-transplant results will be conducted after a year.

Since invasive surgery is not required for stem-cell therapy, the fatality risk is significantly lowered for the patient. However, other risks such as severe bleeding and infections still remain, given the patients weakened condition.

NUH also noted that the stem-cell therapy does not replace liver transplants, and the latter remains the best available treatment for liver cirrhosis.

It is very painful to turn patients away when we cannot offer them a liver transplant, said Dr Dan, adding that this stem cell therapy will serve as an alternative option.

We hope that this is a stepping stone to trials for stem cell candidates, he added.

MORE WAITING FOR A LIVER

The number of people on the waiting list for a liver transplant has been growing in recent years. In June last year, it was reported that there were 54 people on the list, more than double the 24 patients in 2011.

Chronic Hepatitis B remains the primary cause of non-alcoholic fatty liver disease, which refers to a range of liver conditions affecting people who drink little to no alcohol. However, obesity has become a contributing factor to the illness as well.

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New NUH study to test stem cells as treatment for liver disease - TODAYonline

Ashli Stempel helped save her brother’s life. She hopes to inspire others. – GazetteNET

A few small scars on Ashli Stempels lower back are the only evidence that a drill burrowed into her hipbone last year at Brigham and Womens Hospital in Boston. The surgery was to harvest the stem cells in her bone marrow to save her older brother Andrew Stempels life.

At age 27, Andrew was diagnosed with cancer of the white blood cells called Hodgkins lymphoma. Donating her bone marrow so that Andrews body could manufacture healthy blood cells, was a small price to pay to give him a shot at survival, Ashli says.

Since the transplant last August after years of treatment and testing Andrew has been cancer-free and Ashli now volunteers periodically in their hometown of Greenfield, where she serves on the Town Council, to spread awareness about this life-saving treatment.

Our bodies are a cure for some cancers, says Ashli Stempel on a recent Saturday as she handsout sign-up forms atGreenfields Energy Park for the Be A Matchnational donor registry. If even one person joins the registry that is awesome.

Its a sunnyday and Stempel, 30,wearing a black and white spaghetti-strap dress stands behind a booth smiling and talking to passersby.

Everybody wants to cure cancer, but I think not everybody understands that we, ourselves, can be the cure for some types of cancers, she says. I can say that I killed cancer and I am pretty excited about that.

In the hollow spaces in a bodys bones, stem cells inside the bone marrow tissue work to create red blood cells, which feed oxygen to the organs, and make white blood cells to fight infections. The bone marrow also produces blood platelets to help form clots but when a cancer of the blood like, leukemia or lymphoma strikes, these life-supporting systems are thrown out of whack, leaving the bodys immune system unable to fight diseases, infection or the cancer.

Chemotherapy and radiation also can kill off bone marrow tissue, leaving patients with more damage to their immune systems, says physician assistant Susanne Smith, donor services clinician at Dana-Farber/Brigham and Womens Hospitals Cancer Center in Boston.

When transplanted into a cancer patients bloodstream, stem cells, a precursor to all the immune system cells in the body, colonize the bones and help fight any remaining cancer, says Smith.

In many cases (a transplant) is the only cure for a leukemia or lymphoma diagnosis chemotherapy can only get a patient so far, says Mary Halet, director of community engagement at the Be The Match Registry, the Minneapolis organization that manages the largest bone marrow registry in the world. But first, a patient must find a tissue match, that is, a donor who has a similar protein marker called the human leukocyte antigen, which is found on most cells in the body.

There are up to 14,000 patients every year who could benefit from a bone marrow transplant, but many of these people will not receive a donation, says Halet. In most cases, the patient will not finda tissue match in his or her own family andmust seek help from a stranger, she says. A patients likelihood of finding a matching bone marrow donor ranges from 66 percent to 97 percentdepending on ethnic background. White patients have a 97 percent chance of finding a match, while black patients only find a match 66 percent of the time.The difference reflects the complexity of the tissues makeup and the number of donors.

Thats why Halets organization promotes recruitment events like the one Ashli Stempel held in Greenfield.

Stempel says she was ecstatic when she found out that she was a match for her brother. She was in her late 20s at the time, a bubbly woman working in communications at Smith College in Northampton, who grew up in a close-knit family.

Her brother, who was working as a retail manager in the Boston area, had discovered a bump on his collarbone.

I woke up one morning and there was a non-painful lump, Andrew Stempel says.

He ignored it for as long as he could before seeing a doctor who diagnosed it as a swollen lymph node caused by Hodgkins lymphoma.

Cancer is a very scary word. I think what you learn going through it is that it is not such a scary word, you can survive, says Ashli Stempel.

The Stempel family had seen that firsthand years earlier when Andrew and Ashlis mother, Deborah, recovered from breast cancer.

Still, that didnt lessen the anxiety for Andrew. As soon as the doctor said the word cancer, he says, his life started to unravel with a battery of experimental drugs, chemotherapy and radiation.

In the begining there was a lot of uncertainty, he says.

Even through his cancer went into remission after a year, doctors did not expect it to remain that way without high doses of chemo or radiation. The plan was to do a bone marrow transplant for long-term survival.

Still, using donated bone marrow meant taking the risk that Andrews body would reject it, which could be fatal.

So, doctors first wanted to try using Andrews own tissue. That would require removing some of his bone marrow, treating it and then injecting it back into his bloodstream.

Within months of the procedure, however, Andrews cancer returned, indicating to doctors that his body wasnt strong enough to fight it on its own.

Ashli was tested via a mouth swab and Andrew was relieved to learn that she was a tissue match.

I was just overwhelmed with happiness, he says.

Ashli went through a month-long screening process to ensure that she was healthy enough to be a donor. People who have infectious diseases like HIV or hepatitis cannot be donors, nor can those with immune systems weakened by autoimmune diseases. Doctors also prefer to use bone marrow from young donors under the age of 44, says Halet. The registry wont accept donors over 60.

When we are young, our immune systems are at their healthiest and the older we get the less robust they are, she says.

It took two years from the time Ashli first learned she was a match for her brother for the transplant to take place.

Not long aftershe woke up from the surgery, Ashli saw the bone marrow that had been taken from her, a two-literjug ofmilky, red liquid. It was whisked away to another partof the hospital where it ended up in a drip bag connected to a vein in Andrews arm.

Doctors saw hisred and white blood cell counts go up immediately after the transplant.

My sisters cells were working, he says. It was amazing.

Even though the transplant was a success, Andrew had to stay in the hospital for a month. Chemotherapy had caused sores in his mouth, he lost his ability to taste food along withhis appetiteand he droppednearly 30 pounds.

It was tough, day to day, but progressively got better, he says.

Since he was essentially receiving a new immune system, like a newborn baby he also had to be shielded from germs, says Ashli.

When his wife, Meghan Stempel, came to visit him, she needed to wear a facemask and gloves. Even when he returned home, he had to be careful. Hetook a year off from his job to recover, spending many afternoons resting on the couch watching TV. After spending months working to building hisstrength back up,he says, most of his weakness has subsided.

I feel a thousand times better, he says.

He is now cancer free and is returning to hisjob as a retail managerat Sherwin Williams this week.

Following her operation, Ashli took off a few weeks from her job in communications at Smith College, but was back on her feet within a couple days. Her hips were sore which meant limping around the house for a short time.

I was in pain, of course, she says. But its a quick recovery.

A few weeks ago Ashli decided to signup for the national bone marrow donor registry through Be A Matchto donate for a second time.

Her name will stay in the system for the foreseeable future. A match could come up or it might never.

Maybe I will be called on to do it again, who knows?

To learn more about becoming a bone marrow donor or to sign up for the registry, go tobethematch.org.

Potential donors can fill out an online form and the registry will mail a mouth swab kit, which can be returned by mail.

If called, a potential donor will undergo a series of blood tests which will evaluate the suitabililty and safety of the match. Though doctors say risks are low for donors, possible complications include infection and bleeding.

Once a donor is cleared, the transplant procedure could occur within a few weeks or a few months, depending on a recommendation from the patients doctor.

The bone marrow transplant is an outpatient procedure for the donor.Recovery time is only a few days anddonors are typically back to their normal routine in two to seven days.

Donors are told their commitment means being willing to devote up to 30 hours spread over four to six weeks to attend appointments and give the donation.

All medical costs for the donation procedure are covered by the National Marrow Donor Program, which operates the Be The Match Registry, or by the cancer patients medical insurance.

Sometime travel is required. Most travel expenses are covered by Be The Match.

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Ashli Stempel helped save her brother's life. She hopes to inspire others. - GazetteNET

Clinical trial for stem-cell therapy to reverse liver cirrhosis – The Straits Times

SINGAPORE - The use of stem cells to reverse liver cirrhosis - or the hardening of the liver - is being explored in a clinical trial.

Conducted by a multi-centre team led by the National University Hospital (NUH), doctors aim to determine if stem cell therapy can improve liver function.

Previously, liver cirrhosis, caused by various diseases such as chronic hepatitis B and non-alcoholic fatty liver disease, was thought to be irreversible.

A liver transplant provides a definitive cure to end-stage cirrhosis.

However, in Singapore, less than 5 per cent of end-stage liver cirrhosis patients receive a liver transplant.

The number of people on the waiting list for a liver transplant has been increasing over the years, according to statistics from the Ministry of Health.

In 2007, there were nine on the waiting list, compared with 57 last year. There are around 50 waiting for a liver transplant this year.

Also, many patients do not fulfil the eligibility criteria to receive a liver transplant due to other health complications or being above the age limit of 70 years.

The $2.6 million study, which was launched on Tuesday (July 11),is funded by the National Medical Research Counciland 46 patients will be recruited for it. It will run for four years and patients will not need to bear the costs of the stem cell treatment.

Stem cells will be taken from a patient's own bone marrow and will be isolated and injected directly into the patient's liver to initiate the repair.

Similar therapy treatments have been conducted overseas in countries such asEgypt and India, although they have not been fully evaluated for efficacy.

Associate Professor Dan Yock Young, a senior consultant in the division of gastroenterology and hepatology at NUH, said: "We are conducting the study in a systematic and scientific mannerto get definitive evidence of the effects of the treatment."

He also notes that the stem cell therapy is not a substitute for a liver transplant. "This treatment is not intended to pull patients off the waiting list, but provide an option for those who are not eligible for a transplant."

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Clinical trial for stem-cell therapy to reverse liver cirrhosis - The Straits Times