Bone Marrow Cells Repair Heart

July 7, 2006

A study conducted by researchers at the McEwen Centre for Regenerative Medicine at Toronto General Hospital has found the heart sends an 'SOS' distress signal after a heart attack to mobilize specific heart repair cells from the bone marrow.

"This is the first step in repairing the heart and in preventing the vicious downward spiral of heart failure in which the heart progressively thins and dilates, eventually causing death," stated Dr. Shafie Fazel, Cardiac Surgery resident at TGH, University of Toronto and lead author of the study. "These cells act like generals in a battlefield," explained Dr. Fazel. "When damaged heart tissue sends out an 'SOS' distress signal, this subset of bone marrow cells mobilizes quickly and stimulates the growth of new blood vessels in the heart." While modern surgical procedures, mechanical help devices, drugs and organ transplantation do help, more than 50% of patients suffering from congestive heart failure die within five years of initial diagnosis.

"Cardiovascular diseases are the most important cause of mortality in the western world," said Dr. Ren-Ke Li, scientist at the McEwen Centre for Regenerative Medicine and Professor of Cardiovascular Surgery at the University of Toronto. "Each year, 70,000 Canadians suffer from a heart attack and many of them are left with crushing disabilities, mainly because the heart muscle is not able to regenerate after a heart attack. This study identifies the method the body employs to repair the heart and provides new therapies to stimulate cardiac regeneration and prevent heart failure in patients who have suffered a heart attack," noted Dr. Li, who is also a Canada Research Chair in Cardiac Regeneration. The research was performed in Dr. Li's laboratory.

The study was conducted on genetically-engineered mice. Bone marrow cells in the research specimen were modified to carry a green fluorescent market that allowed researchers to track the cells. Following a heart attack, researchers found these bone marrow cells are quickly mobilized to the damaged heart region. Upon reaching the damaged area the cells produce chemicals that trigger the growth of new blood vessels which in turn start the process of repairing the heart.

It was also discovered that a specific molecule, called c-kit, located on the surface of a subset of bone marrow cells plays a central role in the mobilization. This molecule c-kit acts as the 'switch' the 'SOS signals' sent by the damaged heart turn on. Another molecule known as the stem cell factor acts as the key to the turned on c-kit lock. These two molecules combine to activate the bone marrow cells to migrate to the heart for helping growth of new blood vessels.

In the study, mice were separated into two groups -- one with defective c-kit bone marrow cells and the other with normal ones. The mice with defective c-kit bone marrow cells could not mobilize these cells to regenerate the injured heart and faced impaired heart function. In about 42 days after the heart attack, their hearts dilated to twice the size of the normal mouse heart. But if the c-kit cells were restored with normal ones, the heart regeneration process kicked in quickly, confirming the importance of these cells in repairing the heart. This suggests infusion of bone marrow cells after a heart attack may prevent progression of heart failure in patients who survived a heart attack.

The study also showed why some patients have milder heart attacks while others faced more serious ones. "We know that the number of c-kit positive cells decreases with age and elderly patients don't recover from heart attacks as well as younger patients. The key for the older patients would be to find new ways to restore this particular subset of cells in their bone marrow," said Dr. Fazel.

"These findings have very important implications," noted Dr. Richard Weisel, Director of the Toronto General Research Institute, Professor and Chairman of Cardiac Surgery at the University of Toronto and co-author in this study. "Based on the knowledge we gained from this study, we can now design new strategies to enhance normal repair and regeneration for patients who suffered a heart attack."

These research findings can provide a guiding concept for the new field of regenerative medicine which is aimed at restoring, repairing and regenerating damaged organs instead of merely treating the symptoms of disease. The results of the study were recently published in The Journal of Thoracic and Cardiovascular Surgery.

Copyright © 2005 Soflution Ltd.

This article posted August 26, 2006.