Early work on bone marrow cells to heal fragile hearts showed only modest effects. But new research looks at different types of stem cells. 'We're trying to tear pages out of nature's playbook,' says a Chicago cardiologist.
Hoping for a more direct approach that could generate new tissue, Marbán started studying stem cells that come from the heart instead of from bone marrow.
These so-called cardiac progenitor cells naturally repair heart muscle — but they do so far too slowly "to cope with a catastrophic injury" like a heart attack, Marbán says.
The cells are also rare, accounting for about 1 in every 40,000 working heart cells, he estimates. But in larger concentrations, they might be able to speed up the healing process.
To find out, Marbán is leading a trial involving patients who have suffered heart attacks within the past month. First a cardiologist threads a catheter through a patient's neck and into his heart to collect "little snippets of tissue," Marbán says. Those are then cultured in the lab for about a month, until the initial population of cardiac progenitor cells grows to tens of millions. Finally, they're infused back into the patient's heart through another catheter.
The hope is that the cardiac stem cells will take root and reverse the scar. Results should be out later this year. "Let's just say we're extremely encouraged," Marbán says. "It looks like it's working, and cleanly."
Multipurpose cells
In other labs, researchers are focused on more powerful, pluripotent stem cells that have the potential to grow into any type of tissue in the body. Some labs are using embryonic stem cells, and others are studying induced pluripotent stem cells derived from adult tissues and rewound to an embryonic-like state.
"The only cell type that becomes a heart cell is a pluripotent stem cell," says Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at UC San Francisco. If bone marrow stem cells or cardiac progenitor cells do manage to create new heart muscle, he says, "it will be a tiny amount."
But research involving pluripotent stem cells is still preliminary. At the Harvard Stem Cell Institute in Boston, Dr. Kenneth Chien has grown mouse embryonic stem cells into a strip of mature cardiac tissue. But Chien's "heart patch," described in a 2009 edition of the journal Science, was only six to seven cell layers thick — too thin to work as a graft or grow blood vessels. He says he is now developing a three-dimensional cardiac muscle patch "akin to a heart Band-Aid."
Any therapy derived from pluripotent stem cells is a long way from being ready to test in humans. Among other technical hurdles, replacement tissues grown from embryonic stem cells run the risk of rejection, just as with organ transplants. In addition, the same forces that make both types of stem cells so flexible also mean they have the potential to generate tumors. When pluripotent stem cells are used to grow heart cells, researchers have encountered difficulty getting them to beat in sync with surrounding heart tissue.
So some of the most promising work with pluripotent stem cells isn't about making replacement heart tissue but finding other ways to ramp up the heart's own healing abilities. For example, Srivastava's lab has identified three genes that convert connective cells in the heart called fibroblasts directly into cardiomyocytes. Murry calls the research, which was published last year in the journal Cell, a potential "game changer."
Northwestern's Losordo has been studying stem cell treatments for about 14 years. He agrees that the best approach might be to apply what scientists have learned about creating stem cells to turn back the clock within a person's own body. "If you can make a patient's own cell behave as if it's younger, problem solved."
These so-called cardiac progenitor cells naturally repair heart muscle — but they do so far too slowly "to cope with a catastrophic injury" like a heart attack, Marbán says.
The cells are also rare, accounting for about 1 in every 40,000 working heart cells, he estimates. But in larger concentrations, they might be able to speed up the healing process.
To find out, Marbán is leading a trial involving patients who have suffered heart attacks within the past month. First a cardiologist threads a catheter through a patient's neck and into his heart to collect "little snippets of tissue," Marbán says. Those are then cultured in the lab for about a month, until the initial population of cardiac progenitor cells grows to tens of millions. Finally, they're infused back into the patient's heart through another catheter.
The hope is that the cardiac stem cells will take root and reverse the scar. Results should be out later this year. "Let's just say we're extremely encouraged," Marbán says. "It looks like it's working, and cleanly."
Multipurpose cells
In other labs, researchers are focused on more powerful, pluripotent stem cells that have the potential to grow into any type of tissue in the body. Some labs are using embryonic stem cells, and others are studying induced pluripotent stem cells derived from adult tissues and rewound to an embryonic-like state.
"The only cell type that becomes a heart cell is a pluripotent stem cell," says Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at UC San Francisco. If bone marrow stem cells or cardiac progenitor cells do manage to create new heart muscle, he says, "it will be a tiny amount."
But research involving pluripotent stem cells is still preliminary. At the Harvard Stem Cell Institute in Boston, Dr. Kenneth Chien has grown mouse embryonic stem cells into a strip of mature cardiac tissue. But Chien's "heart patch," described in a 2009 edition of the journal Science, was only six to seven cell layers thick — too thin to work as a graft or grow blood vessels. He says he is now developing a three-dimensional cardiac muscle patch "akin to a heart Band-Aid."
Any therapy derived from pluripotent stem cells is a long way from being ready to test in humans. Among other technical hurdles, replacement tissues grown from embryonic stem cells run the risk of rejection, just as with organ transplants. In addition, the same forces that make both types of stem cells so flexible also mean they have the potential to generate tumors. When pluripotent stem cells are used to grow heart cells, researchers have encountered difficulty getting them to beat in sync with surrounding heart tissue.
So some of the most promising work with pluripotent stem cells isn't about making replacement heart tissue but finding other ways to ramp up the heart's own healing abilities. For example, Srivastava's lab has identified three genes that convert connective cells in the heart called fibroblasts directly into cardiomyocytes. Murry calls the research, which was published last year in the journal Cell, a potential "game changer."
Northwestern's Losordo has been studying stem cell treatments for about 14 years. He agrees that the best approach might be to apply what scientists have learned about creating stem cells to turn back the clock within a person's own body. "If you can make a patient's own cell behave as if it's younger, problem solved."