A cellular solution: Cytori’s “Celution” machine (top) processes a sample of fat—as small as a golf ball or as large as a soda can—to isolate its stem cells and other potentially regenerative cells in less than an hour. After processing the fat, a scientist withdraws a pink slurry into a syringe (bottom). The fluid, which will later be injected into the heart, contains as many as a million stem cells per teaspoon.
Credit: Cytori
Credit: Cytori
Biomedicine
Fat Cells for Broken Hearts
A company is testing whether stem cells from fat could help prevent long-term damage after a heart attack.
During a heart attack, blood vessels that deliver blood to the heart muscle are blocked, and the lack of oxygen slowly kills the tissue. San Diego-based Cytori Therapeutics has developed a treatment that aims to prevent much of that muscle damage before it starts. It works by injecting a concentrated slurry of stem cells and other regenerative cells isolated from the patient's body directly into the heart's main artery within 24 hours after an attack. "Time is muscle. The quicker you get in, the better," says Christopher Calhoun, Cytori's chief executive officer. "You can't do anything about dead tissue, but tissue that's bruised and damaged—that's revitalizable. If you can get new blood flow in there, that tissue comes back to life."
Adult stem cells, which exist in small populations throughout the body, can differentiate to form specific tissue types and are responsible for repairing injuries and replacing dying cells. The prospect of using them to heal damaged heart muscle has tantalized biomedical researchers for more than two decades. If the stem cells come from a patient's own body, there is no risk of rejection. A number of clinical trials in recent years have focused on using stem cells collected from bone marrow, since this potent population can differentiate into both cardiac muscle cells and blood vessel cells, among other types. But marrow stem cells are difficult to collect and somewhat scarce; they must be isolated and then grown in culture before they're injected back into an injured heart. The process can take weeks.
Over the last decade, however, researchers have discovered that fat tissue has its own population of stem cells that are more easily accessible and far more abundant than the ones in bone marrow. A typical sample of bone marrow yields about 5,000 stem cells; a sample of fat, gathered quickly through liposuction, can provide up to 200 times that amount. Fat also contains other cells that may aid the healing process. "My belief is that you need that mixed population of cells in order for this therapy to be effective," says Stuart Williams, director of the Cardiovascular Innovation Institute in Louisville, Kentucky, who is not affiliated with Cytori. "Everybody who is now seeing success with the use of these cells—almost all of them—are using a mixed population."
Cytori has created a portable machine that, in less than an hour, can reduce a sample of fat "about the size of a can of Coke," Calhoun says, to less than a teaspoon of concentrated slurry that Cytori believes contains its most vital elements: stem cells, smooth muscle cells, cells that line blood vessels, and a number of other regenerative cells that can promote growth healing.
"Fat tissue has been used for years by very astute surgeons, who just pulled pieces of fat into areas that weren't healing well," Williams says. "All the data so far has shown that these cells are safe, but beyond that, what are these cells doing? We just don't know."
One benefit of Cytori's therapy is that unlike stem cells derived from bone marrow, it can be used immediately after a heart attack, before much tissue damage has occurred. The regenerative cells from fat appear to release growth factors and other chemicals that prevent cell death, Calhoun says, "by sending out signals that say, 'Don't commit suicide—the cavalry's coming.'" He believes that it's the mixture of different cells, rather than just the stem cells, that are important for repair: "I think it's a group of cells that are reacting to the local environment, signaling back and forth, that help stimulate new blood vessels." Cytori's system is already used in Europe, Japan, and elsewhere for cosmetic enhancement, wound healing, and breast reconstruction surgery. But for cardiac use, the company had to retool its "Celution" machine to create a solution safe enough to be injected directly into the coronary artery without clotting. The procedure is relatively straightforward. When a patient comes to the emergency room after a heart attack, a physician removes a fat sample and runs it through Cytori's machine, where enzymes break down the fat and free up the desired cells in the surrounding matrix. "We've taken a seven-to-eight-hour lab process, validated it, optimized it, and put it in a box. Then each patient gets his own sterile tissue right back," Calhoun says. An hour after the fat is harvested, surgeons place a stent into the patient's coronary artery and deliver the slurry of cells.
The procedure has been tested in a 12-person pilot trial in Europe, and the results seem encouraging: after six months, patients who were given a solution of their own fat-derived stem cells within 12 hours of a heart attack had about half as much dead tissue as those who hadn't had the treatment. That translated into fewer irregular heartbeats, better oxygen delivery, and improved blood flow. (Another trial, for chronic heart failure, also shows potential, and the procedure has been approved in Europe.)
Cytori began a large-scale trial this month and hopes to test the procedure on 360 patients. The company aims to start large-scale clinical trials on heart attack patients in the United States by 2014 and on patients with chronic heart failure even earlier than that.
Fat breakdown: The cells Cytori is interested in live in the spaces between the fat cells. The company’s machine uses enzymes to decompose the fat and free up these cells for harvesting. Credit: Cytori "This cell type holds a lot of potential, and I think it could become a very important treatment for heart attack and [restricted blood flow]," says Keith March, director of the Indiana Center for Vascular Biology and Medicine at Indiana University in Indianapolis. "So the fact that they're starting this trial and have shown good evidence of feasibility and safety is very encouraging—we're anxious to see what it shows. That these cells can be obtained so readily and the procedure done in a point-of-care fashion means that this technology could be affordable and accessible even in areas of the world where highly technical surgery may not be possible."
But it's still early. Clinical trials of stem cells derived from bone marrow have shown mixed results in treating heart disease, and it's unclear whether fat-derived cells will fare better. "If it works, it would be wonderful to have a ready-made source of autologous stem cells," says Richard Schatz, research director of cardiovascular interventions at Scripps Health in San Diego, one of the inventors of the coronary stent. But he and others note that it will take many more trials to determine how effective Cytori's methods are compared with treatments based on marrow stem cells.
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