Kris Boesen’s life changed in an instant. In March 2016, he was driving down a winding road in his Nissan 350Z in Maricopa, a tiny hamlet in California’s San Joaquin Valley. Suddenly, the car fishtailed on the wet street, hit a tree and ricocheted into a telephone pole, crushing the vehicle and knocking Boesen unconscious.

When he woke up in the hospital two days later, Boesen was paralyzed from the neck down, his neck broken and his spinal cord crushed. He was now dependent on others for the simplest of tasks, such as eating and drinking, and he needed two attendants 24/7 to help him go to the bathroom and change his position in bed to prevent pressure ulcers.

Boesen was a few weeks shy of his 21st birthday, a young man making his first tentative steps into adulthood. He worked at an insurance brokerage firm, and he spent his free time lifting weights at a gym, tinkering with cars and hanging out with his girlfriend and pals.

The accident brought it all to a screeching halt. “I was basically just existing,” he later admitted.

But the neurosurgeon who fused Boesen’s neck bones to stabilize his spine offered a ray of hope: Boesen might qualify for an experimental treatment that uses stem cells to repair damaged tissue.

He is one of six patients participating in the clinical trial, which is being conducted at the University of Southern California and five other sites across the country. The trial is in collaboration with Asterias Biotherapeutics, a biotech company in Fremont, Calif., that devised the stem cell technology.

In the past decade, a handful of discoveries have unleashed a flood of research into ways neural stem cells can be used for treating degenerative brain disorders and for brain repair. Scores of laboratories at universities and in private industry are uncovering how to use these cells, which transform into neurons, astrocytes (the cells that regulate transmission of electrical impulses in the brain) and oligodendrocytes (which insulate nerve fibers with a fatty coating). Neural stem cells can help mend brain tissue damaged by strokes and spinal cord injuries and keep neurons alive in degenerative diseases like amyotrophic lateral sclerosis (ALS), Huntington’s, Parkinson’s and Alzheimer’s. Recently, tests in humans using stem cells to treat a range of these neurological disorders have been successful.

But some scientists remain dubious that stem cells can be used to grow new brain tissue. “We can make neural stem cells, but are we clever enough to put the circuits in the right place?” wonders Clive Svendsen, director of the Cedars-Sinai Regenerative Medicine Institute in Los Angeles. He worries that “having an incorrect connection is worse than just doing nothing.” Svendsen is more optimistic about his team’s work involving human tests of a novel stem cell approach to treat ALS, a degenerative motor neuron disease in which cells that transmit messages from the brain and spinal cord to the muscles wither or die.

Challenges in the field certainly remain. While recent human trials have shown tantalizing promise, they’re still at an early stage. Moreover, studies have involved a relatively small number of patients, and scientists aren’t sure what complications may emerge.

Even so, Charles Liu, the bioengineer and neurosurgeon heading the stem cell trial at USC, feels confident about the overall direction of the research. “The idea that you can restore function back to where it was lost is relatively new,” he says broadly, not just concerning stem cells. “This is the first time when all of us dared think it might be possible to regenerate, restore and repair.”

Restoring Lost Function

The modern era of regenerating brain function began in the late 1980s and early ’90s with a battle against Parkinson’s disease. The movement disorder stems from the death of neurons that produce dopamine, a neurochemical that dispatches messages to parts of the brain that control motor skills and coordination. People with Parkinson’s develop tremors, rigidity in the limbs and loss of muscle control, and sometimes exhibit signs of dementia.

To fight the disorder, Swedish researchers pioneered the transplantation of fetal stem cells into the brain. The fetal cells the researchers used came from the brains of aborted fetuses 6 to 9 weeks old. Experts reasoned that since these cells had not yet fully matured, there must be some way to coax them to transform into the neurons that Parkinson’s destroys. Studies published in 1992 showed that the grafts of fetal tissue made a significant difference. In two cases, severely disabled patients who had required round-the-clock care before treatment were able to live independently again.

But scientists were stumped on how to best integrate the cell grafts into the brain’s complex circuitry, where they would be more targeted and do the most good.

Back then, the prevailing wisdom in neuroscience was that adults can’t form new neurons. In 1998, however, a team of American and Swedish scientists announced their discovery that the human brain does indeed generate them. It’s a process called neurogenesis, in which cells continually divide and produce new ones. This finding came on the heels of similar observations in rodents, monkeys and birds. “The door has been opened,” Fred Gage, the research team leader at the Salk Institute for Biological Studies in San Diego, told The New York Times at the time. The finding raised the possibility of harnessing this regenerative capacity to mend damaged brains, which could translate into more effective treatments for Alzheimer’s and Parkinson’s.

But how? Acquiring fetal stem cells was proving difficult. “You needed eight aborted fetuses to get enough tissue,” recalls Svendsen, who was working on his postdoc at the University of Cambridge in his native England at the time. “It struck me as impractical. You’re not going to go around collecting aborted fetuses for thousands of patients.” And although using fetal stem cells wasn’t controversial in Sweden, it was in the United States.

The next logical step was to figure out how neurons are generated and use them to repair or replace damaged cells. Embryonic stem cells seemed to offer a solution. Culled from embryos barely 4 or 5 days old, these cells are versatile shape-shifters that can mature into any type of cell in the body — a trait that’s made them crucial to research. And neural embryonic stem cells are more targeted; in the formative stages of brain development, they can be chemically coaxed into generating neurons that have a host of different functions. Plus, neural stem cells can migrate to brain regions where they’re needed most.

Although British researchers had discovered embryonic stem cells in laboratory animals in 1981, it wasn’t until 1998 that a Wisconsin team announced it had isolated stem cells from human embryos for the first time. It was an achievement many thought would quickly usher in medical advances.

Svendsen, who joined the Cambridge faculty in 1998, was inspired by this work and thought it could apply to his Parkinson’s research. He began looking at how to transform stem cells into neurons that would pump out dopamine. He ran a small pilot study of five people with Parkinson’s. Svendsen injected into their brains a protein known to enhance neural development, called glial cell line-derived neurotrophic factor (GDNF). The treatment stopped dopamine-producing neurons from dying, and the patients’ motor skills markedly improved.

Meanwhile, outside forces were derailing promising studies. In the U.S., the use of embryonic stem cells, often derived from embryos discarded by in vitro fertilization clinics, became a flashpoint of intense political debate. This led to a near-total ban in 2001 of their use in government-funded research, an act that held back advances by about five years, scientists say. Research ground to a virtual standstill because of the lack of institutional and financial support, and the onerous restrictions on how research could be done.

In 2006, Japanese scientists figured out how to reprogram specialized cells, such as those in skin, so that they act like embryonic stem cells. Researchers called them induced pluripotent cells, which are created by enticing cells to turn on genes normally found in embryonic stem cells. This process endows them with pluripotency, or the ability to become any type of cell, including neural stem cells. Just two years earlier, in 2004, California voters bucked the White House and approved Proposition 71, establishing the California Institute for Regenerative Medicine. By 2006, the organization issued its first batch of funding from the $3 billion war chest the legislation allocated. With those two developments, research sputtered back to life.

Scientists then began to grapple with some fundamental issues. For starters, how could researchers turn stem cells into mature cell types? Was there a chemical or genetic signal that induced stem cells to create the complex structures of the body and brain? And which molecules and mechanisms were required to integrate stem cells into an injured brain?

Figuring out the answers proved daunting. Over the past decade, however, scientists have begun to decipher how neurogenesis occurs and the anatomical location where neural stem cells are born and maintained inside the brain. “We now have the ability to culture and isolate stem cells in a much more elegant and sophisticated way,” says Gary Steinberg, a stem cell researcher who heads the neurosurgery department at Stanford University. “We now know much more about how the cells work and how they best become integrated into the circuits in the brain.”

Darkness to Light

“It was like someone was turning the lights on,” recalls Kristin Macdonald, a 60-year-old from Beverly Hills, Calif. Macdonald has retinitis pigmentosa, a genetic disorder that causes a gradual decay of the photoreceptors — the rods and cones — in the retina. This thin layer of tissue at the back of the eye detects light and then converts it into nerve impulses that travel to the brain’s vision centers to form images. As the rods and cones die off, people with the disorder experience night blindness and tunnel vision, and eventually become legally or totally blind.

A gracious blonde with a dazzling smile, Macdonald started losing her sight in her late 20s and was legally blind by her 40s. In June 2015, she became the first patient in North America to receive an eye injection of about half a million retinal progenitor cells. The aim was to repair and possibly replace damaged light-sensing cells.

In the time since her treatment, she has noticed a decided change. She can discern shapes and the faint hue of colors, enabling her to recognize cars parked across the street and navigate her cozy art deco-style apartment with surprising nonchalance. This year, Macdonald received another stem cell shot, this time in her right eye, and she is hopeful her vision will continue to improve. “This has made my whole life brighter,” she says, “and I mean that literally.”

For Henry Klassen, an ophthalmologist at the University of California, Irvine, and the director of the retinitis pigmentosa project, the experiment is the fruition of a dream he’s had since his student days. While in graduate school in the mid-1980s, he transplanted retinal tissue into a newborn rat with impaired vision. After the rat grew to adulthood, he shined a light over the graft site. The animal’s pupil constricted. “The first time it happened, I almost fell off my chair,” Klassen recalls. “The only way the rat could see the light was through the transplant.”

But it was another three decades before Klassen — who has used retinal progenitor cells to restore vision in mice, cats, dogs and pigs — could conduct human trials involving retinitis pigmentosa. While no one in the study has fully regained sight, quite a few of them, like Macdonald, have experienced improvements in their visual acuity. “Even if we could slow down the progression and postpone it so they never actually go completely blind,” Klassen says, “that alone is significant.”

Relief for Stroke Patients

In recent years, stem cell research has made such dramatic leaps that what once seemed like science fiction is becoming reality. In a paper published in June 2016, Canadian scientists revealed that a combination of chemotherapy, which wipes out the patient’s diseased immune system, and stem cells, which regenerate the immune system, halted or lessened symptoms of multiple sclerosis.

The trial, which began in 2001 and spanned 13 years, involved 24 people with a severe form of MS. During that period, the positive results endured. One patient, who could barely walk or feed herself before treatment, has been symptom-free and now drives, kayaks, dances and skis. Still, experts sounded a cautionary note because the chemo can be toxic: One patient died of liver failure, and a second had serious liver complications.

In another paper published in June 2016, a Stanford team led by Steinberg proclaimed that injecting adult stem cells directly into the brains of 18 stroke patients substantially restored motor function in many cases. In the study, a small hole was drilled into the skull of the patient, who was awake and under local anesthesia. Stem cells were injected into regions bordering the damaged brain area. Stroke recovery usually plateaus after six months. After the experimental treatment, the patients’ improvements in daily-activity skills continued for up to three years after their strokes.

One of the people in the study was a 71-year-old woman, paralyzed on her left side. After the procedure, she lifted her left arm at Steinberg’s instruction. “I was astonished,” Steinberg recalls, sitting in his office at Stanford Medical Center in the heart of Silicon Valley. “I thought I must have gotten the exam wrong. I couldn’t believe she got that kind of recovery in 12 hours.”

Also in the study was Sonia Coontz, who, at 31, had a severe stroke that impacted movement of her right arm and leg, and garbled her speech. After receiving the treatment two years ago, she experienced quick relief. She was able to speak clearly and was walking better within days. Coontz has since married, and in September 2016, she gave birth to a healthy boy.

“I did not expect them to recover,” Steinberg admits. Instead of turning into neurons and forming synapses — the junctures where signals pass from one nerve cell to another — the modified stem cells seemed to control swelling and stimulate nerve growth and the formation of new blood vessels, Steinberg says. Following the release of the results, his office was deluged with thousands of emails and phone calls from desperate patients and families. But even though the results were encouraging, the study was not a total success; only seven of the 18 participants experienced significant improvement. Stanford researchers are in the middle of a larger trial (which will involve up to 156 patients) that might provide more definitive answers.

Looking to the Future

After the Maricopa car crash, Kris Boesen spent five weeks at a local hospital. In April 2016, he was ferried to USC’s Keck School of Medicine in Los Angeles for the stem cell surgery. Upon arrival, his muscles from the neck down were largely unresponsive. He was hooked up to a feeding tube. It took three people to seat him on the edge of his hospital bed, with one holding his head. The upright position caused his blood pressure to tank.

Doctors had warned him and his parents there were no guarantees. The stem cell procedure on his spine could rob him of what little mobility he had left, and the foreign tissue could clump together, forming a tumor. But Boesen saw it as his only chance of getting his life back. He clenched a pen in his teeth and signed the consent form.

For Liu, the USC neurosurgeon wielding the scalpel, the operation itself was the culmination of decades of research by scientists around the world. In the operating room, Liu carefully sliced open the skin at the back of Boesen’s neck. He cut open the tough, protective membrane around the thicket of nerve fibers that comprise the spinal cord and made a small nick. He carefully inserted a needle into the tiny incision. Slowly, he emptied the attached syringe — full of a thick, pasty substance composed of 10 million stem cells — into the cavity where Boesen’s spinal cord was crushed.

This type of stem cell, called an oligodendrocyte progenitor cell, is found in the brain and spinal cord. They make myelin, the fatty coating around axons — long, threadlike fibers that relay neural impulses from one cell to the next, activating the circuitry that endows us with the physical and emotional capacity to fully embrace the world. Scientists believe these neural stem cells secrete hormonal steroids or proteins that nurse ailing neurons, preventing them from dying, and stimulate the formation of blood vessels that nourish damaged tissue with nutrients and oxygen. They may even promote new connections between the sickly nerves.

The anesthesiologist had stopped Boesen’s breathing for those precious few minutes so the movement of his lungs wouldn’t disturb his spinal cord during the procedure. Liu held his breath, too.

“That was an extremely sobering moment,” he recalls of those crucial minutes. “We were finally doing human tests, and what we were doing was based on years of rational science. This wasn’t just a Hail Mary pass.”

Within a few days of the stem cell procedure, Boesen was transferred to Keck’s rehabilitation unit. He spent two months doing three hours of therapy every day, which included practicing simple daily activities, like piloting his motorized wheelchair and feeding and dressing himself. After three weeks, his recovery was surpassing expectations.

Living in Bakersfield, Calif., with his family, Boesen can now perform many activities, including hugging his family and girlfriend. He’s even begun to have sensation in his knees and thighs.

Patients may regain some feeling or muscle strength when the swelling of the spinal column goes down, says Ramzi Ben-Youssef, medical director of the rehab unit at Keck. “But when they gain more than that, you have to ask yourself what happened here that did not happen in other cases. Stem cells combined with intensive therapy may be the answer.”

Boesen leans back in his wheelchair in his parents’ airy house. Appearing in a video made by USC to demonstrate his capabilities months after the car crash, he looks dapper in a navy blue golf shirt and a snug baseball cap that corrals most of his thick, dark hair. He fires off a series of texts, then, using both arms, lifts a dumbbell high above his head and returns it to his lap. He flashes a warm, toothy grin.

He plans to return to work and is confident he can lead a relatively normal life. “Thank you,” Boesen says, staring into the video camera, his face clouding with emotion. “Thank you for allowing me to live my life again.”