Stem cells reverse heart damage

A new study says heart damage may be reversible with stem cell therapy without dangerous side effects.

On a June day in 2009, a 39-year-old man named Ken Milles lay on an exam table at Cedars-Sinai Medical Center in Los Angeles. A month earlier, he'd suffered a massive heart attack that destroyed nearly a third of his heart.

"The most difficult part was the uncertainty," he recalls. "Your heart is 30% damaged, and they tell you this could affect you the rest of your life." He was about to receive an infusion of stem cells, grown from cells taken from his own heart a few weeks earlier. No one had ever tried this before.

About three weeks later, in Kentucky, a patient named Mike Jones underwent a similar procedure at the University of Louisville's Jewish Hospital. Jones suffered from advanced heart failure, the result of a heart attack years earlier. Like Milles, he received an infusion of stem cells, grown from his own heart tissue.

"Once you reach this stage of heart disease, you don't get better," says Dr. Robert Bolli, who oversaw Jones' procedure, explaining what doctors have always believed and taught. "You can go down slowly, or go down quickly, but you're going to go down."

Conventional wisdom took a hit Monday, as Bolli's group and a team from Cedars-Sinai each reported that stem cell therapies were able to reverse heart damage, without dangerous side effects, at least in a small group of patients.

In Bolli's study, published in The Lancet, 16 patients with severe heart failure received a purified batch of cardiac stem cells. Within a year, their heart function markedly improved. The heart's pumping ability can be quantified through the "Left Ventricle Ejection Fraction," a measure of how much blood the heart pumps with each contraction. A patient with an LVEF of less than 40% is considered to suffer severe heart failure. When the study began, Bolli's patients had an average LVEF of 30.3%. Four months after receiving stem cells, it was 38.5%. Among seven patients who were followed for a full year, it improved to an astounding 42.5%. A control group of seven patients, given nothing but standard maintenance medications, showed no improvement at all.

"We were surprised by the magnitude of improvement," says Bolli, who says traditional therapies, such as placing a stent to physically widen the patient's artery, typically make a smaller difference. Prior to treatment, Mike Jones couldn't walk to the restroom without stopping for breath, says Bolli. "Now he can drive a tractor on his farm, even play basketball with his grandchildren. His life was transformed."

At Cedars-Sinai, 17 patients, including Milles, were given stem cells approximately six weeks after suffering a moderate to major heart attack. All had lost enough tissue to put them "at big risk" of future heart failure, according to Dr. Eduardo Marban, the director of the Cedars-Sinai Heart Institute, who developed the stem cell procedure used there.

The results were striking. Not only did scar tissue retreat -- shrinking 40% in Ken Milles, and between 30% and 47% in other test subjects -- but the patients actually generated new heart tissue. On average, the stem cell recipients grew the equivalent of 600 million new heart cells, according to Marban, who used MRI imaging to measure changes. By way of perspective, a major heart attack might kill off a billion cells.

"This is unprecedented, the first time anyone has grown living heart muscle," says Marban. "No one else has demonstrated that. It's very gratifying, especially when the conventional teaching has been that the damage is irreversible."

Perhaps even more important, no treated patient in either study suffered a significant health setback.

The twin findings are a boost to the notion that the heart contains the seeds of its own rebirth. For years, doctors believed that heart cells, once destroyed, were gone forever. But in a series of experiments, researchers including Bolli's collaborator, Dr. Piero Anversa, found that the heart contains a type of stem cell that can develop into either heart muscle or blood vessel components -- in essence, whatever the heart requires at a particular point in time. The problem for patients like Mike Jones or Ken Milles is that there simply aren't enough of these repair cells waiting around. The experimental treatments involve removing stem cells through a biopsy, and making millions of copies in a laboratory.

The Bolli/Anversa group and Marban's team both used cardiac stem cells, but Bolli and Anversa "purified" the CSCs, so that more than 90% of the infusion was actual stem cells. Marban, on the other hand, used a mixture of stem cells and other types of cells extracted from the patient's heart. "We've found that the mixture is more potent than any subtype we've been able to isolate," he says. He says the additional cells may help by providing a supportive environment for the stem cells to multiply.

Other scientists, including Dr. Douglas Losordo, have produced improvements in cardiac patients using stem cells derived from bone marrow. "The body contains cells that seem to be pre-programmed for repair," explains Losordo. "The consistent thing about all these approaches is that they're leveraging what seems to be the body's own repair mechanism."
This is unprecedented, the first time anyone has grown living heart muscle.
Dr. Eduardo Marban, Cedars-Sinai Heart Institute

Losordo praised the Lancet paper, and recalls the skepticism that met Anversa's initial claims, a decade ago, that there were stem cells in the adult heart. "Some scientists are always resistant to that type of novelty. You know the saying: First they ignore you, then they attack you and finally they imitate you."

Denis Buxton, who oversees stem cell research at the National Heart, Lung and Blood Institute at the National Institutes of Health, calls the new studies "a paradigm shift, harnessing the heart's own regenerative processes." But he says he would like to see more head-to-head comparisons to determine which type of cells are most beneficial.

Questions also remain about timing. Patients who suffer large heart attacks are prone to future damage, in part because the weakened heart tries to compensate by dilating -- swelling -- and by changing shape. In a vicious circle, the changes make the heart a less efficient pump, which leads to more overcompensation, and so on, until the end result is heart failure. Marban's study aimed to treat patients before they could develop heart failure in the first place.

In a third study released Monday, researchers treated patients with severe heart failure with stem cells derived from bone marrow. In a group of 60 patients, those receiving the treatment had fewer heart problems over the course of a year, as well as improved heart function.

A fourth study also used cells derived from bone marrow, but injected them into patients two to three weeks after a heart attack. Previous studies, with the cells given just days afterward, found a modest improvement in heart function. But Monday, the lead researcher, Dr. Dan Simon of UH Case Medical Center, reported that with the three-week delay, patients did not see the same benefit.

With other methods, there may be a larger window of opportunity. At least in initial studies, Losordo's bone marrow treatments helped some patients with long-standing heart problems. Bolli's Lancet paper suggests that CSCs, too, might help patients with advanced disease. "These patients had had heart failure for several years. They were a wreck!" says Bolli. "But we found their stem cells were still very competent." By that, he means the cells were still capable of multiplying and of turning into useful muscle and blood vessel walls.

Marban has an open mind on the timing issue. In fact, one patient from his control group e-mailed after the study was complete, saying he felt terrible and pleading for an infusion of stem cells. At Marban's request, the FDA granted special approval to treat him. "He had a very nice response. That was 14 months after his heart attack. Of course that's just one person, and we need bigger studies," says Marban.

For Ken Milles, the procedure itself wasn't painful, but it was unsettling. The biopsy to harvest the stem cells felt "weird," he recalls, as he felt the doctor poking around inside his heart. The infusion, a few weeks later, was harder. The procedure -- basically the same as an angioplasty -- involved stopping blood flow through the damaged artery for three minutes, while the stem cells were infused. "It felt exacfly like I was having a heart attack again," Milles remembers.

Milles had spent the first weeks after his heart attack just lying in bed re-watching his "Sopranos" DVDs, but within a week of the stem cell infusion, he says, "I was reinvigorated." Today he's back at work full time, as an accounting manager at a construction company. He's cut out fast food and shed 50 pounds. His wife and two teenage sons are thrilled.

Denis Buxton says the new papers could prove a milestone. "We don't have anything else to actually regenerate the heart. These stem cell therapies have the possibility of actually reversing damage."

Bolli says he'll have to temper his enthusiasm until he can duplicate the results in larger studies, definitive enough to get stem cell therapy approved as a standard treatment. "If a phase 3 study confirmed this, it would be the biggest advance in cardiology in my lifetime. We would possibly be curing heart failure. It would be a revolution."
(CNN) 

»»  read more

Sitting may boost cancer risk

Sitting for long periods of time may increase cancer risk, say researchers who recommend the avoidance of prolonged sedentary periods and stress the importance of regular exercise.

The research was presented this week at the American Institute for Cancer Research annual conference in Washington.
Sitting time is emerging as a strong candidate for being a cancer risk factor, researchers say.Sitting time is emerging as a strong candidate for being a cancer risk factor, researchers say. Paul Chiasson/Canadian Press
Christine Friedenreich, an epidemiologist at Alberta Health Services, estimated that lack of physical activity is linked to nearly 100,000 cases of breast and colon cancer in the U.S. each year.
Based in part on those findings, the institute is urging people to make time for physical activity and break every hour of sitting with one to two minutes of activity.
Friedenreich's findings from the Alberta Physical Activity and Breast Cancer Prevention trial were also published in the October issue of the journal Cancer Prevention Research.
In the study, 320 women aged 50 to 74 were randomly assigned either to work up to exercising five days a week for at least 45 minutes or else to continue with their usual inactivity.
Friedenreich found differences in a marker of inflammation, known as C-reaction protein, over 12 months for exercisers compared with controls.
Inflammation markers
The study suggested that it isn't just lack of exercise that increases markers of inflammation, but that a sedentary lifestyle does, too.
Research is starting to point to how exercise may lower markers of inflammation, which in turn might lower cancer risk. But the possible links need to be investigated more thoroughly.
"Sitting time is emerging as a strong candidate for being a cancer risk factor in its own right. It seems highly likely that the longer you sit, the higher your risk," said Neville Owen, head of behavioural epidemiology at Australia's Baker IDI Heart and Diabetes Institute, who also presented findings at the conference.
"This phenomenon isn't dependent on body weight or how much exercise people do," Owen added in a release.
Owen's study measured waist circumference, insulin resistance and inflammation in adults who wore accelerometers to record their physical activity levels. Taking breaks as short as one minute was tied to lower levels of those biomarkers.
The institute offered these tips to help people fit in more activity:
Set the timer on your computer to remind you every 60 minutes that it's time to step away from your desk and take a short walk down the hall.
"Walk with me." Got a quick thing to discuss with a co-worker? Instead of sending an email, ask him or her to join you for a walk to hash it out on the go.
Keep light hand weights in your office to use while reading email or talking on the phone.
During phone calls and phone meetings, stand up and walk around.
Your office or cubicle wall is all you need for simple activities like stretches, vertical push-ups and leg lifts.
 For a more vigorous activity break, ask your employer to put a punching bag or chin-up bar in your break room.

CBC News

»»  read more

Pythons' big hearts hold clues for human health

You don't think of pythons as big-hearted toward their fellow creatures. They're better known for the bulge in their bodies after swallowing one of those critters whole. But the snakes' hearts balloon in size, too, as they're digesting _ and now scientists are studying them for clues about

WASHINGTON (AP) — You don't think of pythons as big-hearted toward their fellow creatures. They're better known for the bulge in their bodies after swallowing one of those critters whole.
But the snakes' hearts balloon in size, too, as they're digesting — and now scientists are studying them for clues about human heart health.
The expanded python heart appears remarkably similar to the larger-than-normal hearts of Olympic-caliber athletes. Colorado researchers report they've figured out how the snakes make it happen.
"It's this amazing biology," said Leslie Leinwand, a molecular biologist at the University of Colorado Boulder, whose team reports the findings in Friday's edition of the journal Science. "They're not swelling up. They're building (heart) muscle."
Reptile biologists have long studied the weird digestion of these snakes, especially the huge Burmese pythons that can go nearly a year between meals with no apparent ill effects. When they swallow that next rat or bird — or in some cases deer — something extraordinary happens. Their metabolism ratchets up more than 40-fold, and their organs immediately start growing in size to get the digesting done. The heart alone grows a startling 40 percent or more within three days.
Leinwand, who studies human heart disease, stumbled across that description and saw implications for people. An enlarged human heart usually is caused by chronic high blood pressure or other ailments that leave it flabby and unable to pump well. But months and years of vigorous exercise give some well-conditioned athletes larger, muscular hearts, similar to how python hearts are during digestion.
So Leinwand's team — led by a graduate student who initially was frightened of snakes — ordered a box of pythons and began testing what happens to their hearts.
The first surprise: A digesting python's blood gets so full of fat it looks milky. A type of fat called triglycerides increased 50-fold within a day. In people, high triglyceride levels are very dangerous. But the python heart was burning those fats so rapidly for fuel that they didn't have time to clog anything up, Leinwand said.
The second surprise: A key enzyme that protects the heart from damage increased in python blood right after it ate, while a heart-damaging compound was repressed.
Then the team found that a specific combination of three fatty acids in the blood helped promote the healthy heart growth. If they injected fasting pythons with that mixture, those snakes' hearts grew the same way that a fed python's does.
But did it only work for snakes? Lead researcher Cecilia Riquelme dropped some plasma from a fed python into a lab dish containing the heart cells of rats — and they grew bigger, too. Sure enough, injecting living mice made their hearts grow in an apparently healthy way as well.
Now the question is whether that kind of growth could be spurred in a mammal with heart disease, something Leinwand's team is starting to test in mice with human-like heart trouble. They also want to know how the python heart quickly shrinks back to its original size when digestion's done.
The experiments are "very, very cool indeed," said James Hicks, a biologist at the University of California, Irvine, who has long studied pythons' extreme metabolism and wants to see more such comparisons.
If the same underlying heart signals work in animals as divergent as snakes and mice, "this may reveal a common universal mechanism that can be used for improving cardiac function in all vertebrates, including humans," Hicks wrote in an email. "Only further studies and time will tell, but this paper is very exciting."
The study was funded by the National Institutes of Health and a Boulder biotechnology company that Leinwand co-founded, Hiberna Corp., that aims to develop drugs based on extreme animal biology.

AP

»»  read more

Health/Daily Ginger Dose May Reduce Risk of Colorectal Cancer

A daily dose of ginger could reduce colon inflammation and ultimately help reduce the risk of colorectal cancer, a new study suggests.

Researchers found that study participants who took ginger supplements had a 28 percent decrease in one measure of colorectal inflammation, compared with those who took a placebo. Studies have shown that people with higher levels of rectal inflammation are more likely to develop lesions, which can develop into cancer.
The researchers noted that the study was small — it had only 30 participants — and more research is needed into ginger's effect on cancer risk.
Still, "the results look promising," said Patricia Thompson, a professor of cellular and molecular medicine at the University of Arizona Cancer Center, who was not involved in the study.
The second-deadliest cancer
Colorectal cancer, which can grow in both the colon and the rectum, kills more people annually in the U.S. than any other cancer except lung cancer. The National Cancer Institute estimated that 142,000 people in the U.S. were diagnosed with colon cancer in 2010, and 51,000 died from the disease.
Other research has examined ways to lower the risk of developing colorectal cancer. For example, regularly taking aspirin can reduce your colorectal cancer risk, but it can also lead to gastrointestinal bleeding. And some studies suggest certain foods, such as cherries and black raspberries, lower colorectal cancer risk, but none have tested ginger in people, Thompson said.
So far, the best way to prevent colorectal cancer is to get screened, she said.
In the new study, the researchers looked at how levels of a substance called PGE2 changed, along with other signs of inflammation in the colon, when people took daily doses of ginger extract.The researchers randomly assigned the 30 participants to take either two grams of ginger root supplements or a placebo once a day for 28 days.
PGE2 is a hormone-like molecule your body releases when an area of the body becomes inflamed.
The study participants were all healthy people, who had a "normal" risk of developing colorectal cancer, said study researcher Suzanna Zick, an assistant research professor at the University of Michigan Medical School.
When Zick and her team compared rectal biopsies of the participants they took at the beginning and end of the study, they found that PGE2 levels decreased an average of 28 percent in those taking ginger, but were nearly unchanged in those taking the placebo. Side effects for the two treatments were mild and included headache, fatigue and gastrointestinal problems, such as bloating, gas and nausea, the researchers said. [7 Side Effects of Cancer Treatment, and How to Cope With Them]
Many questions remain
Zick said that another, larger trial is needed to corroborate her study's findings and to answer the host of questions the study raised.
In particular, future research will need to figure out how ginger might reduce rectal PGE2 levels. If ginger acts to reduce inflammation the same way as a class of drugs called COX-2 inhibitors, then it may also share the drugs’ downside of increasing a person’s risk for cardiovascular disease, Zick said.
We also don't know how much ginger a person would need to take to possibly reduce their cancer risk, Thompson said. In the study, the researchers chose two grams of ginger extract, which equates to about 20 grams of raw ginger root, because past trials showed that this dose is the highest a healthy person can tolerate — more ginger would increase gastrointestinal problems.
Despite the unknowns, "the research is very exciting," said Thompson. “Given the effect seen in such a small study suggests that this effect is very big — more research will show just how big.”
The study was published Oct. 11 in the journal Cancer Prevention Research.
Pass it on: Eating ginger may reduce your risk of developing colorectal cancer, but don’t go stocking up on ginger root just yet — more research is still needed.

Photo by iStock| Story by MyHealthNewsDaily

»»  read more

Super Broccoli to Fight Cancer

A "super broccoli" developed by British scientists to fight cancer and heart disease goes on sale Tuesday.

The vegetable contains high levels of a nutrient thought to protect against the life-threatening diseases.

The broccoli - called Beneforte - will be sold at the UK retailer Marks & Spencer starting Tuesday and will be on the shelves of other supermarkets next year.

Studies have shown men with broccoli-rich diets have a reduced risk of prostate and bowel cancer. Other research suggests it can also help prevent heart attacks and strokes.

Beneforte contains three times the amount of the beneficial plant chemical glucoraphanin than normal strains of broccoli.

It was created using conventional methods at the Institute of Food Research and John Innes Center in the UK. Work on the project began after a wild broccoli variety was discovered in 1983 with raised levels of glucoraphanin.

The nutrient is converted in the stomach into sulphoraphane, which scientists believe will stop the uncontrolled cell division associated with early-stage cancer.

"Our research gives insight into broccoli's role in promoting health," said Professor Richard Mithen of the IFR.

Science minister David Willetts said the research would give "a real boost to agriculture, personal health and the economy."

»»  read more

Fair-skinned people 'may need to take extra vitamin D supplements'

Pale-skinned people who are prone to sunburn may need to take vitamin D supplements, according to a new research.

The researchers at the Leeds University say that those with very pale skin may be unable to spend enough time in the sun to make the amount of vitamin D the body needs while also avoiding sunburn.

Their study suggests patients with the skin cancer melanoma may in particular need vitamin D supplements.

The researchers, however, cautioned that sunlight and supplements are not the only factors that can determine the level of vitamin D in a person's body.

The study defined the optimal amount of vitamin D required by the body as at least 60nmol/L.

However, at present there is no universally agreed standard definition of an optimal level of vitamin D.

"Fair-skinned individuals who burn easily are not able to make enough vitamin D from sunlight and so may need to take vitamin D supplements," Professor Julia Newton-Bishop, lead author of the study based in the Cancer Research UK Centre at the University of Leeds, said.

"This should be considered for fair-skinned people living in a mild climate like the UK and melanoma patients in particular," she said.

Researchers took the vitamin D levels of around 1,200 people and found that around 730 people had a sub-optimal level.

They found that those with fair-skin had significantly lower levels.

»»  read more