Combination of nanoparticles and stem cells cleans, heals clogged vessel walls, study shows

By Amanda Gardner
HealthDay Reporter

GoogleNews.com, USNews.com/health, WEDNESDAY, July 21 (HealthDay News) — A two-step procedure that uses nanoparticles to first scrub plaque out of arteries and then inserts stem cells to promote healing of those arteries may one day help individuals with atherosclerosis, new research suggests.

“One of the problems of removing plaque [with current methods such as angioplasty] is that there is damage to the underlying wall,” explained Dr. Edward A. Fisher, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Medical Center, in New York City, who was not involved with the research. “The rate of restenosis [when the vessel closes over again] is very high.”

This new technique, performed only in pigs so far, would circumvent that problem with this “somewhat provocative ability to heal the vessel wall by administering stem cells after you injure the vessels,” Fisher said. “If this were true in people, it could be an option for the future.”

The research, conducted by Russian scientists, was presented Tuesday at the American Heart Association’s Basic Cardiovascular Sciences — Technological and Conceptual Advances in Cardiovascular Disease meeting, in Rancho Mirage, Calif.

Nineteen pigs were divided into three groups, all receiving tiny nanoparticles either with or without stem cells (the stem cells were also delivered in one of two different ways). A second set of 18 pigs received salt water instead of nanoparticles.

The nanoparticles were delivered directly into the pigs’ hearts, then heated with lasers to clear out the accumulated plaque, a procedure referred to as “nanoburning.”

Six months after the procedure, plaque volume was reduced an average of 56.8 percent in the pigs receiving nanoparticles vs. an increase of 4.3 percent in the control group.

Pigs who had received both nanoparticles and stem cells showed the greatest improvements, along with signs of artery healing, the study authors found.

Three of the pigs who received nanoparticles delivered by microbubbles (as opposed to intracellularly or with a patch attached to the heart) experienced blood clots, the researchers reported.

Right now, drug-eluting stents appear to be quite successful in treating atherosclerosis, said Fisher, but the new technique might one day be helpful in two particular subgroups: People who form clots after receiving a drug-eluting stent and who now require long-term anti-platelet therapy, and diabetic patients who are difficult to treat with angioplasty and stenting.

However, studies with animals that show promise don’t always guarantee that the benefits will be seen in humans.

The Ural State Medical Academy in Yekaterinburg, Russian Federation, funded the study, with help from private investors.

A second study, from German researchers, used stem cells to heal tissue after a heart attack, although that research, Fisher said, “is a few steps more removed from clinical practice [than the nanoparticle study].”

Thirty rats were outfitted with miniature plastic scaffolds coated with stem cells engineered to overexpress different types of cytokines. Cytokines are cells produced by the immune system that facilitate communication between cells.

Other rats were given a cytokine-related gene and still others received stem cells without the scaffolding.

Rats who were implanted with scaffolding plus genetically modified stem cells saw greater improvements in blood pressure function than those in the control group, according to the report by Dr. Matthias Siepe, assistant professor and staff surgeon at the department of cardiovascular surgery, Medical University Center in Freiburg, Germany, and colleagues.

Both trials are preliminary, though, noted Dr. Darwin J. Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White in Temple, the Stearman Chair in Genomic Medicine and a professor of molecular and cellular medicine in the College of Medicine.

“Other clinical trials [into using stem cells for heart repair] are going on, but how well they’re doing I don’t quite know and the basis for understanding how they work is still not quite there,” he said.

For more on using stem cells to repair a damaged heart, visit the U.S. National Institutes of Health.

The Cancer-Causing Sex Virus
Matthew Herper, 07.22.10

Martin Duffy, a Boston consultant and economist, thought he just had a sore throat. When it persisted for months, he went to the doctor and learned there was a tumor on his tonsils.

Duffy, now 70, had none of the traditional risk factors for throat cancer. He doesn’t smoke, doesn’t drink and has run 40 Boston marathons. Instead, his cancer was caused by the human papilloma virus (HPV), which is sexually transmitted and a common cause of throat and mouth cancer.

HPV tumors have a better prognosis than those caused by too many years of booze and cigarettes. But Duffy “is in the unlucky 20%” whose cancer comes back–despite rounds of chemotherapy and radiation that melted 20 more pounds off a lean 150-pound frame. Now the cancer has spread throughout his throat, making eating and talking difficult. “I made my living as a public speaker,” he says. “Now I sound like Daffy Duck.” Duffy believes he has only a few months left. “How do you tell the people you love you love them?” he asks.

Most strains of the HPV virus are harmless, but persistent infections with two HPV strains cause 70% of the 12,000 cases of cervical cancers diagnosed annually in the U.S. Other forms of the sexually transmitted virus can cause penile and anal cancer, and genital warts. The HPV throat cancer connection has emerged in just the last few years and is so new that the government doesn’t track its incidence. Researchers believe it is transmitted via oral sex. But top researchers estimate that there are 11,300 HPV throat cancers each year in the U.S.–and the numbers are growing fast as people have been having more sexual partners since the 1960s. By 2015 there could be 20,000 cases. For more surprising discoveries about HPV, read here.

These big numbers have some top researchers arguing that drug makers should test whether HPV vaccines now used to prevent cervical cancer in women can also prevent throat infections in boys. Two vaccines, Gardasil from Merck and Cervarix from GlaxoSmithKline, are approved for preventing cervical cancer. Gardasil is approved for use in boys only to prevent genital warts.

Vaccinating boys could stop this meteoric increase in throat cancer. “Clearly, boys need to be vaccinated,” says Marshall Posner, the incoming medical director of head and neck cancer at Mt. Sinai Medical Center in New York. “I want my kids to be vaccinated. I don’t see a downside to these vaccines.”

There’s only one problem: The vaccine manufacturers aren’t terribly hot on the idea. GlaxoSmithKline says it has no plans to study throat cancer. It adds that it is “committed to providing a vaccine specifically designed to protect against cervical cancer in girls and young women.”

Merck, the maker of Gardasil, seemed more interested a couple of years ago. In 2008 it funded Maura Gillison, the Ohio State University researcher who established the HPV-throat-cancer link in 2000, to do a pilot study to show that test could reliably detect HPV infection in the throat. The pilot study was successful. By early 2009 Gillison says that a larger study of the vaccine in throat cancer looked close to being green lit.

But after Merck agreed to buy rival Schering-Plough for $41 billion in March 2009, interest in a big study seemed to evaporate, Gillison says. In a statement, Merck says that “due to competing research and business priorities, we decided not to move ahead with an efficacy study at this time.”


The drug makers’ reticence probably stems from a fear that a throat-cancer vaccine would be hard to get approved. Papilloma viruses usually cause cancer slowly, causing pre-cancerous lesions that take many years to blossom into full-fledged malignant tumors. Papilloma viruses cause the horn-like growths in rabbits that probably gave rise to myths of “jackalopes” in the American West. In the cervix, early abnormal growths can be picked up with a diagnostic test, the Pap smear. Clinical trials of Gardasil and Cervarix took advantage of this, measuring the number of pre-cancerous growths prevented by the vaccines.

But there are no easy-to-detect pre-cancers in the throat. Adolescent boys would have to be followed for decades to to see if the vaccine prevented throat cancer, an unlikely scenario. Short of this, studies could only look at the prevention of HPV throat infections, not cancer or cancer precursors directly. Approving a vaccine for wide use based on this type of short-term data would require a leap of faith that the Food and Drug Administration might not be willing to take.

Top researchers say the federal government needs to step in and fund the long study if drug companies cannot be persuaded to do it themselves. “I’m sorry Merck decided not to do it,” says Posner. “But in the end, this is a federal responsibility. It’s a public health issue.”

For his part, Martin Duffy thinks that drug companies’ complacent attitude toward throat cancer would be different if more of their employees were in his situation. “It will change real fast,” he says, “if one of their executives comes down with this disease.”

HPV–known for causing cervical cancer–is emerging as the leading cause of throat cancer in men. Should they get the vaccine too?

Nine Things You Need To Know About HPV
1. HPV is the most common sexually transmitted infection.

At least 20 million Americans have HPV, and 6 million become infected each year. Most HPV infections are harmless, but a few of the 40 known HPV strains can cause cancer (mainly cervical cancer) or warts.

2. There are HPV vaccines.

Gardasil, from Merck, protects against four HPV strains and prevents pre-cancerous cervical lesions in women and genital warts in both sexes. Cervarix, from GlaxoSmithKline, protects only against two strains that cause cervical cancer, and also protects against pre-cancerous lesions.


3. HPV is a global scourge.

Worldwide, HPV is the second-biggest cause of cancer death, according to the World Health Organization. Half a million women are infected every year, and 288,000 die, with nearly 80% in the developing nations in Asia, Africa and Latin America.

4. Pap smears reduce the toll from HPV.

There are 12,000 cases of cervical cancer annually in the U.S., and the disease kills 4,000 women a year. Forty years ago, it was the leading cause of death in women, but the Papanicolau smear, a diagnostic test, helped reduce the toll.

5. HPV throat cancer is surging.

A new form of throat cancer is cased by HPV, and will afflict 2,300 women and 9,000 men this year. By 2015 there could be 20,000 cases, according to some estimates.
6. HPV causes other cancers.

In the U.S. each year HPV causes 3,700 cases of vulvar cancer, 1,000 cases of vaginal cancer, 1,000 cases of penile cancer, 2,700 cases of anal cancer in women and 1,700 cases of anal cancer in men.

7. HPV throat cancer has a good prognosis.

Throat cancers caused by HPV are much less deadly than the traditional kind of head-and-neck cancer, which is brought on by years of heavy smoking and drinking. Patients with the HPV form survive five years 80% of the time. For non-smokers, the rate is above 90%, according to recent research.

8. Most teenage girls don’t get the vaccine.

Gardasil is recommended by the CDC but is not mandatory. Thanks to public distrust of drug companies and perhaps the vaccine’s high cost, only 34% of girls ages 13 to 17 have received the vaccine, according to a recent study in the American Journal of Preventative Medicine.

9. We’re in a quandary over whether to vaccinate men.

Gardasil and Cervarix should protect against throat cancer, too. But while it was possible to test whether they would prevent precancerous cervical cancer, such a study is impossible with throat cancer. That means that the vaccines may never receive FDA approval for throat cancer prevention.

© Jurate/iStock