heart attack

Regenerating damaged muscle after a heart attack

/ Kevin McCormack / Leave a comment

Cardio cells image

Images of clusters of heart muscle cells (in red and green) derived from human embryonic stem cells 40 days after transplantation. Courtesy UCLA

Every year more than 735,000 Americans have a heart attack. Many of those who survive often have lasting damage to their heart muscle and are at increased risk for future attacks and heart failure. Now CIRM-funded researchers at UCLA have identified a way that could help regenerate heart muscle after a heart attack, potentially not only saving lives but also increasing the quality of life.

The researchers used human embryonic stem cells to create a kind of cell, called a cardiac mesoderm cell, which has the ability to turn into cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells. All these types of cells play an important role in helping repair a damaged heart.

As those embryonic cells were in the process of changing into cardiac mesoderms, the team was able to identify two key markers on the cell surface. The markers, called CD13 and ROR2 – which makes them sound like extras in the latest Star Wars movie – pinpointed the cells that were likely to be the most efficient at changing into the kind of cells needed to repair damaged heart tissue.

The researchers then transplanted those cells into an animal model and found that not only did many of the cells survive but they also produced the cells needed to regenerate heart muscle and vessels.

Big step forward

The research was published in the journal Stem Cell Reports. Dr. Reza Ardehali, the senior author of the CIRM-funded study, says this is a big step forward in the use of embryonic stem cells to help treat heart attacks:

“In a major heart attack, a person loses an estimated 1 billion heart cells, which results in permanent scar tissue in the heart muscle. Our findings seek to unlock some of the mysteries of heart regeneration in order to move the possibility of cardiovascular cell therapies forward. We have now found a way to identify the right type of stem cells that create heart cells that successfully engraft when transplanted and generate muscle tissue in the heart, which means we’re one step closer to developing cell-based therapies for people living with heart disease.”

More good news

But wait, as they say in cheesy TV infomercials, there’s more. Ardehali and his team not only found the markers to help them identify the right kinds of cell to use in regenerating damaged heart muscle, they also found a way to track the transplanted cells so they could make sure they were going where they wanted them to, and doing what they needed them to.

In a study published in Stem Cells Translational Medicine,  Ardehali and his team used special particles that can be tracked using MRI. They used those particles to label the cardiac mesoderm cells. Once transplanted into the animal model the team was able to follow the cells for up to 40 days.

Ardehali says knowing how to identify the best cells to repair a damaged heart, and then being able to track them over a long period, gives us valuable tools to use as we work to develop better, more effective treatments for people who have had a heart attack.

CIRM is already funding a Phase 2 clinical trial, run by a company called Capricor, using stem cells to treat heart attack patients.

 

UCLA Study Suggests New Way to Mend a Broken Heart

/ cirmweb / 2 Comments

When you suffer a heart attack, your heart-muscle cells become deprived of oxygen. Without oxygen, the cells soon whither and die—and are entombed within scar tissue. And once these cells die, they can’t be brought back to life.

But maybe—just maybe—there is another way to build new heart muscle. And if there is, scientists like Dr. Arjun Deb at the University of California, Los Angeles (UCLA), are hot on the trail to find it.

Scar forming cells (in red) in a region of the injured heart expressing blood vessel cell marker in green and thus appearing yellow (see arrows). This study observed that approximately a third of the scar-forming cells in the injured region of the heart adopted "blood vessel" cell-like characteristics. [Credit: Dr. Arjun Deb/Nature]

Scar forming cells (in red) in a region of the injured heart expressing blood vessel cell marker in green and thus appearing yellow (see arrows). This study observed that approximately a third of the scar-forming cells in the injured region of the heart adopted “blood vessel” cell-like characteristics. [Credit: Dr. Arjun Deb/Nature]

Published yesterday in the journal Nature, Deb and his team at UCLA’s Eli & Edythe Broad Center for Regenerative Medicine and Stem Cell Research have found some scar-forming cells in the heart have the ability to become blood vessel-forming cells—if given the proper chemical ‘boost.’

“It is well known that increasing the number of blood vessels in the injured heart following a heart attack improves its ability to heal,” said Deb. “We know that scar tissue in the heart is associated with poor prognosis. Reversing or preventing scar tissue from forming has been one of the major challenges in cardiovascular medicine.”

Tackling the ever-growing problem in heart disease can seem an almost insurmountable task. While heart disease claims more lives worldwide than any other disease, advances in modern medicine in recent decades mean that more and more people are surviving heart attacks, and living with what’s called ‘heart failure,’ for their hearts can no longer beat at full capacity, and they have trouble taking long walks or even going up a flight of stairs.

Transforming this scar tissue into functioning heart muscle has therefore been the focus of many research teams, including CIRM grantees such as Drs. Deepak Srivastava and Eduardo Marbán, who have each tackled the problem from different angles. Late last year, treatment first designed by Marbán and developed by Capricor Therapeutics got the green light for a Phase 2 Clinical Trial.

In this study, Deb and his team focused on scar-forming cells, called fibroblasts, and blood-vessel forming cells, called endothelial cells. Previously, experiments in mice revealed that many fibroblasts literally transformed into endothelial cells—and helped contribute to blood vessel formation in the injured area of the heart. The team noted this phenomenon has been called the mesenchymal-endothelial transition, or MEndoT.

In this study, the researchers identified the molecular mechanism behind MEndoT—and further identified a small molecule that can enhance this transition, thus boosting the formation of blood vessels in the injured heart. This study bolsters the idea of focusing on the creation of blood vessels as a way to help reverse damage caused by a heart attack. Said Deb:

“Our findings suggest the possibility of coaxing scar-forming cells in the heart to change their identity into blood vessel-forming cells, which could potentially be a useful approach to better heart repair.”

Protein Drip Spurs Stem Cells to Save Heart Tissue

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When you suffer a heart attack, beating heart muscle cells become deprived of oxygen and die—and become encased in scar tissue. Once these cells die, they can’t be brought back to life. But new research presented this week has found that injecting a protein into the heart immediately following an attack can spur stem cells to repair the damaged heart tissue.

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Presenting at this week’s Society of Nuclear Medicine and Molecular Imaging’s Annual Meeting in St. Louis, MO, researchers from the Gunma Prefectural Cardiovascular Center in Maebashi, Japan, have found that a protein called G-CSF—when injected into the hearts of patients who recently suffered an attack—can actually spur a type of bone marrow stem cells to migrate to the heart and curb the spread of cellular death that normally takes place.

Previous research had revealed that administering G-CSF improves the heart’s ability to pump blood. In this study, the team wanted to understand how G-CSF could do so in a patient who just suffered a heart attack. Dr. Takuji Toyoma, the study’s lead author, explained in a news release:

“This study shows that the first intravenous drip infusion of G-CSF during treatment just after hospitalization was able to rescue our patients. I am confident that with additional data from a forthcoming clinical trial, this protocol can be adopted as a standard of practice.”

In this study, the researchers gathered 40 patients who had recently suffered an acute heart attack. They gave half of them an intravenous G-CSF for a period of five days, while the others received a saline solution. A year’s worth of imaging and stress tests then revealed that the earlier the G-CSF was administered, the greater the improvement in blood flow and overall cardiac function.

As Toyoma explained above, the next steps involve a forthcoming clinical trial where the precise effects of G-CSF, including the timing of when best to administer the protein, can be determined.

The research team’s preliminary efforts hold promise in the fight against heart disease. While heart disease is still the world’s number one killer, recent medical advances have increased the chances of surviving an attack. However, for those that do survive they often must live with heart failure—their hearts unable to beat at full capacity.

Many scientists, including a variety of researchers supported by CIRM, have therefore looked to regenerative medicine to regenerate lost heart muscle. The findings presented by Toyoma and his team point to another avenue by which stem cells could be harnessed to improve the quality of lives for those who have experienced a heart attack, and maybe prevent their slide into heart failure.

Protein Drip Spurs Stem Cells to Save Heart Tissue

/ cirmweb / Leave a comment

When you suffer a heart attack, beating heart muscle cells become deprived of oxygen and die—and become encased in scar tissue. Once these cells die, they can’t be brought back to life. But new research presented this week has found that injecting a protein into the heart immediately following an attack can spur stem cells to repair the damaged heart tissue.

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Presenting at this week’s Society of Nuclear Medicine and Molecular Imaging’s Annual Meeting in St. Louis, MO, researchers from the Gunma Prefectural Cardiovascular Center in Maebashi, Japan, have found that a protein called G-CSF—when injected into the hearts of patients who recently suffered an attack—can actually spur a type of bone marrow stem cells to migrate to the heart and curb the spread of cellular death that normally takes place.

Previous research had revealed that administering G-CSF improves the heart’s ability to pump blood. In this study, the team wanted to understand how G-CSF could do so in a patient who just suffered a heart attack. Dr. Takuji Toyoma, the study’s lead author, explained in a news release:

“This study shows that the first intravenous drip infusion of G-CSF during treatment just after hospitalization was able to rescue our patients. I am confident that with additional data from a forthcoming clinical trial, this protocol can be adopted as a standard of practice.”

In this study, the researchers gathered 40 patients who had recently suffered an acute heart attack. They gave half of them an intravenous G-CSF for a period of five days, while the others received a saline solution. A year’s worth of imaging and stress tests then revealed that the earlier the G-CSF was administered, the greater the improvement in blood flow and overall cardiac function.

As Toyoma explained above, the next steps involve a forthcoming clinical trial where the precise effects of G-CSF, including the timing of when best to administer the protein, can be determined.

The research team’s preliminary efforts hold promise in the fight against heart disease. While heart disease is still the world’s number one killer, recent medical advances have increased the chances of surviving an attack. However, for those that do survive they often must live with heart failure—their hearts unable to beat at full capacity.

Many scientists, including a variety of researchers supported by CIRM, have therefore looked to regenerative medicine to regenerate lost heart muscle. The findings presented by Toyoma and his team point to another avenue by which stem cells could be harnessed to improve the quality of lives for those who have experienced a heart attack, and maybe prevent their slide into heart failure.