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A “Smart” Way to Repair Damaged Tissue, Pages 1–3) Volume 4, Issue 1 2009 The Beat™ A Compendium of Information About the University of Ottawa Heart Institute HIGHLIGHTS “ The concept of using cell-based therapy to rebuild blood vessels in and around the heart is proving to be the next frontier in cardiac medicine. This landmark devel- opment clearly represents a major step forward in adding to our ability to cure heart failure.” – Dr. Marc Ruel, Director, Cardiac Surgery Laboratory, UOHI (from A “Smart” Way to Repair Damaged Tissue, pages 1–3) “ What we are trying to do is to figure out which genetic pathways are lost or activated as we age to see if that capacity for repair can be recreated in the adult heart.” – Patrick Burgon, UOHI researcher (from Regenerative Medicine, page 3) The Heart Institute’s Ottawa Model for Smoking Cessation is considered the most advanced approach in Canada for identifying and treating tobacco addiction. Researchers at the University of Ottawa Heart Institute have developed a smart scaffold that one day may help repair damaged heart tissue following a heart attack. In this image of tissue from a rat’s hind limb, progenitor cells have been recruited to form new blood vessels to (from Playing a Pivotal Role: support the growth of muscle tissue. The Heart Institute Leads New Approaches to Clinical Care, page 3) The electron microscopy expertise of the Stewart Whitman Histology Core Laboratory is generating a lot of A “Smart” Way to outside interest and paying clients. (from Canada Beats a Path to Heart Institute Core Pathology, page 4) Repair Damaged Tissue A heart attack is an emergency event, but carried towards the heart until it hits a Surgery Laboratory, Erik Suuronen and once the immediate danger has passed, the narrowing in the artery. The plaque his Heart Institute colleagues have developed damage can be long-lasting. Heart tissue becomes lodged and, suddenly, the flow of a way to support and enhance the heart’s may die, compromising cardiac function, oxygen-rich blood to the heart is blocked. innate capacity to regenerate itself. IN THIS ISSUE while the scar tissue that forms as a result doesn’t conduct electrical signals the What we’ve just witnessed is the onset of a There are two aspects to regenerating lost P. 1–3 A “Smart” Way to Repair way healthy muscle does. This can lead heart attack. The lack of oxygen, known tissue. One is to regrow muscle that will Damaged Tissue to potentially dangerous arrhythmias. as ischemia, damages the tissue normally contract like normal heart tissue. But for Researchers at the University of Ottawa P. 3 Playing a Pivotal Role: The Heart Institute Heart Institute have developed a smart Leads New Approaches biomaterial that promises to help the body UOHI researchers have developed a way to Clinical Care repair tissue damaged by impaired blood flow associated with heart attacks and to support and enhance the heart’s innate P. 4 Canada Beats a Path to Heart other conditions such as diabetes. Institute Core Pathology capacity to regenerate itself. The Beat is published by the University of Ottawa Let’s take a look, for a moment, inside the Heart Institute (UOHI). Comments or questions chest of a person with coronary artery fed by the blocked blood vessel. Muscle that to happen, you also need new blood about The Beat should be directed to Jacques Guérette, Vice President, Communications, disease. Among other things, we can see cells start to die and heart tissue can be vessels to feed that growing tissue. While at 613-761-4850 or [email protected]. that there are yellowy patches in the permanently lost. The heart has a main- research is underway to effectively regrow For more information about UOHI, please visit arteries. These are plaque deposits that tenance system for replacing cells that muscle, studies have shown that generating www.ottawaheart.ca. have accumulated in the artery walls over regularly die off, but the amount of new blood vessels — a process known as © 2009 University of Ottawa Heart Institute many years. As we watch, a piece of plaque damage caused by a heart attack over- revascularization — on its own helps The Beat is a trademark of the University breaks free from one of these deposits. whelms that system. Working with of Ottawa Heart Institute. It tumbles along in the bloodstream Dr. Marc Ruel, Director of the Cardiac (continued on page 2) 2 Repairing Damaged Muscle: A) A collagen matrix containing sialyl Lewisx is injected at the site of damaged muscle tissue, where it gels to form a smart scaffold. B) The presence of sialyl Lewisx attracts progenitor cells to the site and binds with their L-selectin receptors. The progenitor cells take up residence in the scaffold, where they begin to differentiate and form new blood vessels. C) The new vessels provide oxygenated blood to growing muscle tissue, repairing the damage caused by ischemia. (A “Smart” Way to Repair Damaged Tissue, continued) restore cardiac function. Suuronen’s work the regeneration process. This combined focuses on the revascularization process. effort greatly increases the extent of EPC The key, he has found, is helping mobilization. Sialyl Lewisx also improves progenitor cells do their job. EPC survivability so the cells have more The results showed that the rats time to fully engraft and differentiate. One of the cell types that replenish blood The biomaterial is liquid when cool, vessels is known as endothelial progenitor making it easily injectable at the damaged receiving the smart scaffold had a cells (EPCs). They are undifferentiated site. It then gels at body temperature to cells originating in bone marrow that the form the stable scaffold. 90 per cent increase in blood flow to body calls on when damage occurs. Signals go out to attract EPCs to a damaged site. To test their creation, the researchers Once they arrive, the progenitor cells can induced ischemia in thigh muscle in the the damaged tissue compared with become or stimulate the growth of new hind limbs of rats. They then treated some blood vessels, supplying oxygen to support rats with the smart scaffold and gave new muscle growth. Unfortunately, EPCs others collagen alone. The results showed the collagen-only rats. are not abundant, so by itself, the body that the rats receiving the smart scaffold can accomplish only so much repair. had a 90 per cent increase in blood flow to the damaged tissue compared with the One hope of scientists has been to give the collagen-only rats. The treated rats also system a boost by externally introducing had improved functioning after two weeks progenitor cells to increase their numbers. and showed no increase in inflammatory To date, the results of these cell therapies response. These results were published have been less successful than originally online in January by The FASEB Journal expected. Instead of introducing cells (Erik Suuronen et al., FASEB J. 2009 from the outside, the biomaterial devel- Jan 9. [Epub ahead of print]). oped by Suuronen’s group expands the capacity of the body’s own regenerative The success of this approach opens the door process. “Our goal,” Suuronen explained, to a variety of applications. Because the “is to develop safe and effective treatments smart scaffold enhances the body’s natural for coronary artery disease by helping the regenerative process, it could be paired body rebuild blood vessels and improve with several current and future inter- heart function.” ventional strategies to increase their impact. These include angioplasty, cell Three things need to happen for EPCs to transplant therapies, and the transplan- become new blood vessels. They need to tation of heart muscle tissue grafts. be called into action and released into the ErikErik Suuronen,Suuronen, PhDPhD bloodstream through cell signalling; they “The concept of using cell-based therapy need to be recruited to and retained at the to rebuild blood vessels in and around the damaged site; and they need to be kept heart is proving to be the next frontier in alive and active long enough to transform cardiac medicine. This landmark devel- into new vascular tissue. opment clearly represents a major step forward in adding to our ability to cure The new biomaterial addresses each of heart failure,” said Dr. Ruel. these issues. It consists of a collagen matrix “ Our goal is to develop safe and effective treatments that has been modified to increase its Added Suuronen, “We see this as a for coronary artery disease by helping the body strength and longevity. Collagen is the breakthrough that may also positively main component of connective tissue in impact diseases such as diabetes, some rebuild blood vessels and improve heart function.” the body. The matrix provides a scaffold disorders of the liver and chronic brain where EPCs can reside while they go ischemia.” This close collaboration between • Scientist, Division of Cardiac Surgery, University of Ottawa Heart Institute through the process of differentiation. scientist and cardiac surgeon is indicative of the Heart Institute’s integration of • Research Investigator, Molecular Function & Imaging Program, A carbohydrate molecule known as sialyl research and clinical practice. As this work University of Ottawa Heart Institute x Lewis puts the “smart” in the scaffold. progresses, the partnership will help • Associate Professor, Department of Surgery; cross-appointment with the This molecule binds and retains EPCs translate successful research into patient Department of Cellular and Molecular Medicine, University of Ottawa where they are needed. In turn, the therapies more quickly. j progenitor cells then release protein • Research interests: treatment of cardiac injury and disease using tissue engineering and cell-based approaches; stem cell response to heart messengers called cytokines that travel tissue damage j through the circulatory system and to the bone marrow.
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