Announcements - Fighting heart disease with fat

March 2, 2009 — Winnipeg, Manitoba

Most people would like to lose it. But thanks to NRC research, body fat — or adipose tissue — may some day become a valuable medical resource for repairing damaged hearts.

Heart infarction — the death of heart muscle — is the leading cause of heart failure, affecting an estimated 350,000 Canadians annually. It ranks as the number one cause of hospital admissions in Canada.

"If a significant portion of your heart muscle is dead or too weak to support the body, the only real therapeutic choice is heart transplantation," says Dr. Ganghong Tian, a senior researcher at the NRC Institute for Biodiagnostics (NRC-IBD) in Winnipeg. "Unfortunately, there's a limited donor pool available for heart transplants. Across Canada, fewer than 200 heart transplantations are performed each year. As a result, a significant percentage of heart-failure patients die while waiting for heart transplantation."

Magnetic resonance image of a pig heart. Circled area shows implanted stem cells in the anterior wall of the left ventricle.

One possible solution is to transplant stem cells into an injured heart. Today, most researchers in the field of tissue regeneration are focusing on embryonic stem cells and bone marrow stem cells. But Dr. Tian and his colleagues believe that adipose-derived stem cells (ASCs) show great promise for repairing damaged hearts.

"Many people carry excess fat, so there's no shortage of fat tissue," explains Dr. Tian. "Many people voluntarily go to the hospital to ask physicians to remove their fat, but you don't see anyone going to the hospital to ask physicians to remove their bone marrow. Most people find it more acceptable to use stem cells from fat tissue than embryonic stem cells for heart repair."

Adipose-derived stem cells offer other benefits, too.

Dr. Ganghong Tian leads NRC efforts to develop adipose-derived stem cells for heart transplantation.

"We've found the density of stem cells collected from fat tissue is at least ten times higher than the density of stem cells from bone marrow," says Dr. Tian. "Also, ASCs have the potential to differentiate into various cell types, including heart cells. Moreover, ASCs grow faster than bone marrow stem cells. As a result, if you need to grow stem cells outside the body, ASCs could generate a clinically relevant cell dose in a much shorter period of time than bone marrow stem cells do."

More importantly, NRC research suggests that ASCs can, indeed, repair damaged heart muscle. "In our studies, we take a rat or pig, open its chest and then block a coronary artery that supports the heart to induce a heart attack," says Dr. Tian. "One week later, we open the animal's chest again and inject stem cells. We then monitor the animals for up to six months. In the experimental group, the heart contractions are much stronger — pumping more blood out to the body — compared to animals that undergo blockage of a coronary artery but no stem cell transplantation."

While ASCs do improve heart function, the amount of improvement is limited, stresses Dr. Tian. "In our study, we injected five to ten million stem cells into either rat or pig hearts, but 95 percent of the ASCs migrated out of the heart while less than 5 percent of the implanted cells stayed in the heart. The limited protection they offer seems to be related to the very limited number of cells that you can successfully transplant into the heart. If we can find a way to get more stem cells to stay in the heart, we may see better heart function," he adds.

In the fall of 2008, a multidisciplinary research team led by Dr. Tian was awarded a five-year, $1.25 million grant from the Canadian Institutes of Health Research to address this issue. With collaborators at St. Boniface General Hospital, the Health Sciences Centre of the University of Manitoba, Queens' University and the NRC Steacie Institute for Molecular Sciences, the team aims to develop new techniques to deliver ASCs more efficiently to the heart or other organs.

"In order to track ASCs with magnetic resonance imaging (MRI), we load these cells with tiny magnetic iron particles that make them visible as tiny spots," says Dr. Tian. "If we put a strong magnet outside the chest, could that help ASCs stay in place?"

With help from other researchers at NRC, he and his colleagues hope to develop "nano-particles" that are more magnetic than commercially available iron particles, as well as a new magnet that generates a stronger magnetic field. "Our ultimate goal is to be able to inject stem cells into a leg or arm vein rather than directly into the heart and, with the help of a magnet, increase the proportion of stem cells that accumulate in the heart," says Dr. Tian. "Alternatively, if a patient has a stroke or brain injury, we could design a magnet that generates a very strong magnetic field in the brain to help accumulate stem cells there."