Stem cells placed in a scaffolding generate a brand new rat heart outside the body.
Image: The University of Minnesota
Wearing white jeans and a navy shirt bejeweled with glittering stars, 15-year-old Paizley Carwell-Bowen lounges in the living room of her family’s North Hollywood apartment. She seems like a typical bubbly teenager —she chats and giggles with a girlfriend, she dreams of being a pop star—but she has a troubled past. “Sometimes I’d see the devil,” she says.
Paizley’s disturbing visions started after she had a stroke at age 6. The stroke was just one complication of sickle-cell anemia, the hereditary disease that has haunted her since infancy. Most common among people of African descent, the disorder causes oxygen-carrying red blood cells, which are normally flexible and round, to become rigid and take on a crescent (or sickle) shape. Sickle cells have trouble squeezing through fine blood vessels to deliver oxygen to the body’s tissues and organs. Instead they clump and choke off blood flow, causing intense pain as bits of lung, bone, brain, and kidney succumb to a lack of oxygen. Those with the disease die slowly, over years.
Paizley was so sick that doctors told her parents she might not live to be 18. Her early stroke left her left leg partially paralyzed. The pain would upend her days and nights. Her hip joints began to erode. She missed so much school due to hospitalizations that by age 11 she had been held back two grades. Then things got even worse. Her doctors tried to prevent another stroke by giving her blood transfusions every three weeks to dilute her sickle cells with normal red blood cells. The scheme worked for a number of years, but Paizley’s immune system learned to identify proteins on the transfused blood cells and began to attack them. Her own body was working at full speed to destroy the blood that was intended to save her life.
After a while it was virtually impossible to find blood for transfusion that could slip past Paizley’s ever-alert immune system. The prognosis was grim. “We were running out of options,” says Hisham Abdel-Azim, one of her doctors at Children’s Hospital of Los Angeles. He and his colleagues ultimately told Paizley and her parents that there was only one hope left: a risky stem cell transplant. Using powerful chemotherapy drugs, they would wipe out the bone marrow that produced the faulty sickle cells. Then they would transfuse donor bone marrow rich in the highly prized stem cells that are capable of generating new, normal blood. The family took the gamble.
Now, almost four years later, it is hard to imagine that Paizley is the same person. And in a critical way, she isn’t. Although she was born with sickle-cell genes, she no longer has sickle-cell disease. The healthy blood that flows through her veins is not her own; it is that of a 45-year-old woman who donated her marrow. Her body was rebuilt with that stranger’s stem cells, and Paizley now sleeps at night pain-free. She does not need blood transfusions. She no longer worries about having another stroke or dying young. She attends school uninterrupted. The devil is at bay.
WAITING FOR MIRACLES
Paizley’s recovery highlights just one minuscule part of the potential of stem cells, the immortal progenitor cells that endlessly divide, generating new tissue throughout a person’s life. The stem cells used to treat Paizley, specific to the blood, came from the bone marrow of a healthy adult donor. But even more far-ranging treatments may be possible with embryonic stem cells, the blank-slate cells that give rise to all organs and tissue types and that (theoretically) can repair all forms of organic damage and disease. These endlessly malleable cells were first isolated from embryos by University of Wisconsin scientists in 1998. Since then, they have been touted as the cure for nearly every disease, and even as the antidote to aging and death.
The early concept about how to harness these cells was simplicity itself: Harvest the unformed cells from embryos and inject them into needy recipients. The stem cells would then start rebuilding damaged hearts, pushing cancer to remission, or healing injured spinal cords. Multiple sclerosis, lupus, arthritis, even psychiatric illnesses would all be swept away under the tidal wave of the stem cell cure.
Given the grandeur of the vision, is it any wonder that when research stalled, frustration grew? As the paralyzed lived out their lives in wheelchairs, as loved ones faded into the netherworld of Alzheimer’s, as cancer and heart disease struck with impunity, calls for cures grew louder: Where are our stem cell therapies? Why have we had to wait so long?
For a long time, the answer appeared to be political, a by-product of the controversy over abortion. The most potent of the stem cells are the most undifferentiated ones, so immature that they are neither skin nor nerve, heart cell nor muscle; they are derived from the embryo in the earliest stages of life. The mother of all stem cells is the zygote, the single cell formed by the fusion of an egg and sperm. Within about five days, the zygote evolves into a blastocyst, a clump of about 150 cells that contains a handful of “pluripotent” cells imbued with the capacity to transform into every type of tissue except placenta. It is at this stage, when the fertilized egg is smaller than the period at the end of this sentence, that researchers extract the inner part of the blastocyst, from which embryonic stem cells are derived.
Once extracted, these flexible human cells are placed on top of a layer of embryonic mouse cells. Under the right conditions, colonies of human cells grow out from the edge. Researchers remove these mechanically and, with some luck, can nurture them into an embryonic stem cell line that lives in perpetuity in the laboratory.
But until recently there was no way to produce those cells without sacrificing an embryo, an act that is considered tantamount to murder by some critics. Moreover, because foreign stem cells would be rejected by the body, much like a foreign heart or kidneys, scientists had proposed literally cloning the patients, in essence creating a duplicate from which cells could be culled in embryonic form. Even though such clones would be just a collection of cells, the concept unleashed a firestorm of criticism, leaving some researchers fearing for their lives.
