Just Add Blood
Are skin cells the new stem cells?
By Lee Fehrenbacher
BRISKLY TRAVERSING a white-walled lab on the fourth floor of UW’s Brotman Building, developmental biologist Dr. Lil Pabon snaps on a pair of green latex gloves and powers up a microscope. A soft blue light flickers to life as Pabon reaches into a refrigerator full of incubating petri dishes. She surveys the contents, grabs one, and sets it beneath the scope. Instantly, a glob of mucous jumps into view on an adjacent computer screen. Then—out of nowhere—it beats. Ba-dum. Like a heart beating. Like a muscle contracting. The screen blurs as the microscope refocuses. Did that slime just move?
ISCRM, the University of Washington’s Institute for Stem Cell and Regenerative Medicine (“Ice Cream” to insiders), is just one of two labs in the country growing heart muscle out of embryonic stem cells. The South Lake Union center’s beating boogers represent the initial stages of a discovery that—for the million Americans who suffer heart attacks each year—may hold the key to life itself.
“Myocardial infarction [heart attack] is the number-one cause of death in the United States,” explains ISCRM’s codirector Dr. Chuck Murry, a bioengineer and pathologist by training. After years of struggling to promote heart attack response awareness (basically: yes, you are having the big one; for God’s sake get to a hospital), Murry decided to focus instead on mending the organ by halting the gradual decay of tissue that leads to fatal heart failure. After an attack—in effect, a clog in the blood flow of an artery that suffocates blood-pumping muscle tissue—the heart scars and turns into dead muscle. If a person is not treated, this leads to new attacks, killing more muscle tissue and ultimately causing organ failure and death. But if you could regrow heart tissue and inject it into the heart, reasoned Murry’s team, you could stop further attacks from occurring. They set about reprogramming stem cells into heart-muscle cells by injecting them with a cocktail of four specific genes, then grew them into muscle tissue.
“I have not yet found the person who is offended by the use of skin cells.”
There was just one problem. Embryonic stem cells are drawn from human embryos, fertilized eggs that carry the capacity for life as well as the ability to save it. But many believe embryonic research is unethical, George W. Bush among them. In 2001, amid a fiery debate surrounding the origins of life, Bush drew a line in the sand, approving 60 existent human embryonic stem cell lines for research purposes, but forbidding government-funded scientists from creating new ones. Of the approved stems, just 21 turned out to be useful in the lab, and it’s those 21 lines that ISCRM uses to grow hearts. As the years go by, however, the lines are aging, making the cells more difficult to program and grow into tissue.
A few months ago the team conducted a study on rats. They induced myocardial infarction in the rodents, then implanted lab-grown tissue into their hearts. Initial results show that the transplanted tissue prevented additional heart failures. They would like to try it on humans, but unless new stem lines become available they may never have enough tissue to heal a human heart.
In the meantime some ISCRMers have begun focusing on the business potential of organ engineering. Dr. Buddy Ratner, director of the UW Engineered Biomaterials Center and an ISCRM researcher, has had a hand in five of the 100 medical device companies that have spun out of the UW in the past 10 years (and into an industry estimated at $100 billion). Redmond-based Healionics currently markets a Ratner biomaterial that may one day be used as fully implantable glucose sensors for diabetics, putting an end to all that finger pricking. He’s also collaborating with an orthopedic surgeon at Harborview Medical Center to create a bio-degradable scaffold that will help humans regrow fingers in the same way a salamander regrows its body parts. As tissue grows around the scaffold, the scaffold biodegrades, leaving only the new finger in its place.
Late last year, an ISCRM discovery sent Murry over the moon: Collaborators in Japan have used his team’s genetic cocktail to grow heart tissue using skin cells instead of stems. “I have not yet found the person who is offended by the use of skin cells,” says Murry, beaming from behind his desk. On top of that, skin cells are about as abundant as the air we breathe. “Imagine we took a skin biopsy from you,” he says, pinching my arm, “grew up some of your cells that we’d reprogrammed with these four genes. Look what they can do.” He spins around a computer monitor displaying a blob of slime that is slowly, steadily, throbbing its way into existence.
Published: August 2008