In early 2009 Mike Jones bought a newspaper at a convenience store in Louisville, Ky., and read about a local doctor who wanted to try something unprecedented: healing an ailing heart by harvesting and multiplying its native stem cells—immature cells with regenerative powers. Jones, then 65, had congestive heart failure: his heart was no longer pumping blood efficiently. He contacted the doctor, Roberto Bolli of the University of Louisville, and in July of that year Jones became the first person in the world to receive an infusion of his own cardiac stem cells.
Before treatment, Jones could barely climb stairs. Today he feels well enough to chop his own firewood and clear fallen tree limbs from his nine-acre property. His “ejection fraction,” a measure of how much blood the heart pumps from one chamber to another, increased from 20 to 40 percent in the two years following the experimental treatment—lower than a typical level (in the 55 to 70 percent range) but still a dramatic improvement.
Since then, hundreds of other patients with heart damage have similarly improved after doctors injected them with stem cells extracted from their own heart or bone marrow, as well as stem cells from unrelated donors. Researchers think the stem cells turn into new tissue and stimulate other cells to divide. Many important questions remain unanswered, however. Scientists still do not know which of the different kinds of stem cells work best and how exactly to prepare the cells before treatment—but they are quickly gaining insights. “I think we are at the dawn of one of the biggest revolutions in medicine in our lifetime,” Bolli says. “We still need to learn how to use these cells properly—but this is real. In the future, we will collect our own stem cells, grow them and keep them in freezers until we need them.”
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Priming the Pump
For the past four decades scientists thought of the human heart as a powerful but vulnerable living pump. Because the adult heart appeared incapable of regenerating its cells, any cell death would irrevocably weaken the organ, researchers reasoned. Now and then, however, a scientist glimpsed adult heart cells dividing under the microscope. Carbon dating of preserved heart tissue has since confirmed that the adult heart replaces its cells throughout life, although this turnover is modest compared with that in the gut and skin. Biologists now estimate that the heart replaces 1 percent or more of its four to five billion muscle cells each year. Researchers have also learned that the new cells arise from duplication of mature heart cells as well as from stem cells embedded in the heart.
These native stem cells allow the heart to repair itself in small ways. After a heart attack, for example, resident stem cells mature into new heart cells and encourage existing cells to divide. This self-repair lasts only a week or two, however, which is not nearly enough time to replace the more than one billion cells lost in a typical heart attack. The result is a large area of inflexible scar tissue. Just as a car tire bulges where it has been damaged, the human heart swells where it has been scarred; the once efficient football-shaped organ becomes a flabby, ineffectual pump.
Stem cell therapy works by giving the heart a mega dose of its own repair cells. Animal studies indicate that some injected stem cells mature into adult cells, but most die within a few days. Before the cells expire, however, they secrete a cocktail of proteins that encourage healthy heart cells to proliferate, as well as enzymes that break down the collagen fibers in scar tissue, making way for new heart muscle.
So far researchers have completed only a few small trials with patients. Bolli and his colleagues harvested a small piece of heart tissue from each of 23 patients with heart damage or failure, including Jones. The researchers nurtured tiny gardens of the heart cells in petri dishes, filtering out stem cells by searching for a stem cell–specific protein marker known as c-kit. They then allowed the stem cells to make millions of copies of themselves.
Sixteen patients received one million cardiac stem cells each via a catheter fed into the coronary artery, and seven patients received standard care (which consisted mainly of beta blockers and diuretics). Four months later the ejection fraction had increased from a starting average of 30.3 percent to an average of 38.5 percent in patients who received stem cells, but it had barely budged in standard care patients (inching from 30.1 to 30.2 percent). One year after treatment the average weight of scar tissue in stem cell patients had decreased by 30 percent.
In a similar trial, Eduardo Marbán of the Cedars-Sinai Heart Institute in Los Angeles and his colleagues treated 17 patients with their own stem cells and another eight patients with standard care. Marbán and his team used remotely controlled forceps to pinch off peppercorn-size specks of heart tissue to grow in the lab. Whereas Bolli had extracted mainly “true” stem cells displaying c-kit from his lab cultures, Marbán extracted a more diverse mixture of cells—some of which may have a more limited repertoire. Patients who received standard care showed no statistically significant change in scar mass or healthy heart tissue. Stem cell patients showed a 42 percent decrease in scar mass and a 13-gram increase in healthy tissue over one year, although their ejection fraction hardly improved.
Other researchers have attempted to treat heart failure with so-called mesenchymal stem cells derived from bone marrow, which are appealing because they are less likely to become cancerous compared with other stem cells. Mesenchymal stem cells secrete growth factors that prompt nearby cells to multiply and can turn into heart muscle in the right environment. Trial results have been inconsistent so far—some patients clearly improve, whereas others show few or no positive changes.
Joshua Hare of the University of Miami wondered if heart patients would tolerate bone marrow stem cells donated by a stranger or reject them as foreign. Hare gave 15 patients injections of their own bone marrow stem cells, and another 15 people donated cells. Thirteen months later none of the patients in either group had rejected the stem cells, and scar tissue had diminished by more than one third in both groups. Elderly patients may benefit more from the stem cells of young donors than from their own because younger cells have not endured as much wear and tear.