Courtesy of USC Trojan Family Magazine
Four days after undergoing major surgery, 21-year-old Kris Boesen picked up a smartphone and sent a text. It was the first message that he had sent in months.
But what was truly remarkable was that a man who was once almost completely paralyzed was holding a phone at all.
It hadn’t always been like this. One night in March changed Boesen’s life. He was driving along a winding stretch of wet road in Maricopa, California, when his white Nissan 350Z fishtailed out of control. The sports car careened into a curb, a tree and then a telephone pole, breaking Boesen’s neck. After the accident, Boesen could only move his left arm up and down, and his hands were stuck in a clenched position. He couldn’t hold a fork to feed himself or use his arms to operate a wheelchair. He couldn’t use his legs, either.
“I was basically just existing,” Boesen says. “I wasn’t really living my life.”
Boesen’s neurosurgeon at the local hospital, who fused his neck bones right after the accident, recognized that Boesen might be a candidate for a new treatment being offered through a clinical trial at Keck Medicine of USC. The surgeon contacted neurologist Charles Liu, director of the USC Neurorestoration Center. Liu’s procedure is part of a clinical trial sponsored by the California Institute for Regenerative Medicine through Asterias Biotherapeutics, and involving five other clinical sites, with a goal of helping people with spinal cord injuries gain independence.
Stem cells, or “blank slate” cells, have the potential to become several kinds of cells in the body. These cells could, in theory, help replace or repair damaged tissues — and after years of lab research, doctors have started to test that theory with patients in clinical trials.
Speaking with Boesen’s family, Liu carefully outlined the operation, which would involve injecting stem cells directly into the young man’s spinal cord. The surgery was meant to demonstrate that the procedure was safe, and the physicians hoped Boesen would gain more movement, as well. As Liu explained, it could make the difference between being almost fully paralyzed or being able to use his arms and hands to control a wheelchair or phone.
But Liu also outlined the risks. Boesen might lose what little arm movement he had. There was also the possibility that the stem cells could form a tumor.
The family waited until Boesen could breathe and speak on his own, so he could weigh the risks and decide whether he wanted to give his consent. A few weeks after the accident, doctors removed his ventilator, and his father told Boesen about the trial.
“Heck, yeah,” he responded. “We’ve got to do this.”
With a pen propped in his hand, he signed his consent with an X.
The stem cells Liu had to offer are called oligodendrocyte progenitor cells. Oligodendrocytes make the crucial insulating material, called myelin, that surrounds the wire-like sections of the body’s nerve cells. Scientists believe that the stem cells not only repair the damaged insulation, but also invite blood vessels back into the injury site. Plus, they release factors that help nourish nerves, potentially reviving nerves that were nearly dead. Asterias Biotherapeutics, based in Silicon Valley, grows the therapeutic cells in a lab.
Liu had to time the surgery just right. In the first weeks after the accident, swelling and inflammation in Boesen’s spinal cord wouldn’t allow the stem cells to survive. After about a month, scar tissue filling the spinal cord would interfere with the cells’ effects.
In early April, a month after his accident, Boesen was wheeled into an operating room at Keck Medical Center of USC. Liu and a surgical team opened the back of Boesen’s neck, cut a nick in the tough membrane surrounding his spinal cord, and slid in a needle. The anesthesiologist stopped Boesen’s breathing, so the motion of his lungs wouldn’t move his spinal cord. Liu held his breath too, as he slowly squeezed 10 million stem cells—thick, like toothpaste—out of the syringe. Then the team waited, watched and hoped.
Liu and his colleagues aren’t alone in their high hopes for stem cell medicine. Across USC’s campuses, nearly 100 scientists, doctors and engineers investigating stem cell therapies are part of the USC Stem Cell initiative. “This is to bring people together who are working in the area of stem cells,” explains Andy McMahon, who leads the initiative. “It takes all sorts of people,” he adds, pointing to the contribution that tissue engineers, developmental biologists, geneticists, clinicians and others can all make to the effort.
Some initiative members are working out the basic biology of stem cells; others are applying that knowledge in the clinic. USC researchers have, collectively, pulled in millions of dollars in grants from the California Institute for Regenerative Medicine.
The heart of the effort is at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, directed by McMahon, which offers the tools that keep research projects humming. USC scientists might use its Chang Stem Cell Engineering Facility to turn a patient’s skin cells into stem cells so they can replicate the person’s disease with cells growing in a dish, or correct disease-causing mutations. They might then take those dishes to the Choi Family Therapeutic Screening Facility to test how different drugs affect the cells. USC’s stem cell research center also has facilities to look at cells under the microscope, sort them based on their characteristics and change their DNA.
For Boesen, being part of the clinical trial was life-changing. Within months he could lift weights, write his name, operate a motorized wheelchair and feed himself. Boesen’s natural recovery process and rehabilitation could have contributed to the improvement, but his recovery has differed significantly from what doctors normally see during treatment for this type of injury, Liu says.
Like anyone steeped in science, Liu is wary of getting too enthusiastic about early results. He’s also careful not to predict the path of Boesen’s progress. The treatment probably won’t reverse an injury so that people like Boesen can walk again, but it’s realistic to hope that a small amount of repair in the spine could translate to big benefits in terms of arm movement.
The stem cell injection was just the start of Boesen’s journey to improved arm motion. Recovery also required hard work in Keck Medicine’s Inpatient Acute Rehabilitation Unit. For two months, the Boesens worked with a team of physical, occupational and speech therapists, as well as physicians, nurses, case managers and social workers. Marisa Hernandez, an assistant professor of clinical occupational therapy, worked with Boesen on basic skills such as brushing his teeth and getting dressed. Wearing his own clothes instead of a hospital gown helped Boesen feel like himself again, Hernandez says. Another big victory: feeding himself at the Panda Express at the USC Health Sciences Campus food court.
Having a positive attitude is a huge factor in working through the intensive therapy, says Ramzi Ben-Youssef, medical director of the rehab unit. Doctors and therapists remarked on Boesen’s cheery outlook. “He’s a jokester, for sure,” says Sheetal Desai, clinical coordinator for the clinical trial at Rancho Los Amigos National Rehabilitation Center, USC’s partner on the study. “Sometimes he’ll pretend that he has to faint. … He likes to give us a scare.”
Boesen is now back at home with his parents in Bakersfield, planning for the future. He wants to return to his career as an insurance broker and live a more independent life. “All of this wouldn’t have been possible without the stem cells,” Boesen says.
The study isn’t over, and the treatment is not yet ready to become a standard therapy. But with promising results from Boesen, as well as others in the trial at different sites, the researchers now plan to double the dose, to 20 million stem cells. They’ll also be treating people with less-severe spinal injuries, who would have been too risky to include in the initial tests for safety because they have more function to lose.
McMahon, who is chair of the Department of Stem Cell Biology and Regenerative Medicine, predicts that stem cell treatments could reach many patients within the next decade. USC already has laid the groundwork for clinical trials exploring stem-cell-based treatments for HIV/AIDS, Alzheimer’s disease, the dry form of age-related macular degeneration, osteoarthritis in the knee and immune system damage due to chemotherapy. Because the therapies would replace damaged tissue with new, healthy tissue, treatments would provide true cures, he says.
And in the far future, Ben-Youssef speculates, the right set of cells and the right techniques might help spinal injury patients even more than they helped Boesen.
After all, when Ben-Youssef and Liu were in medical school, they learned that there was no way to fix the spinal cord—once the nerves were damaged, that was supposed to be it.
“You never know,” Ben-Youssef says.
For information about the clinical trial, visit the SCiStar Study website. Rancho Los Amigos/Keck Medicine of USC is no longer enrolling participants in the clinical trial.