A baby girl, Robbie, is the first human to undergo experimental surgery involving the placement of a stem cell patch that repairs and restores damaged spinal tissue.
The pioneering spina bifida surgery, involving a team of 40 people from the University of California, Davis, happened while Robbie was still developing in his mother’s womb.
As the University of California, Davis researchers describe, this new fetal surgery “could be life-changing for a developing baby with spina bifida, who otherwise could be born paralyzed from the waist down.”
Prior to Robbie’s surgery, the treatment had only been tested on sheep and dogs.
Robbie was beating his legs shortly after he was born. Which is a great sign.
What is spina bifida?
Spina bifida, also known as myelomeningocele, is a neural tube defect that occurs early in pregnancy when the spine and spinal cord do not form properly.
The neural tube is the structure of a developing embryo that eventually becomes the brain, spinal cord, and the tissues around them.
The defect can lead to a range of cognitive, motor, urinary and intestinal disabilities throughout life. Some children spend their lives in wheelchairs.
Surgery after birth can help reduce some of the effects – while surgery before childbirth can prevent or lessen the severity of damage to the fetal spine, which worsens during pregnancy.
Long to come
The surgery was part of a clinical trial involving 35 babies.
The trial is led by Diana Farmer, the world’s first female fetal surgeon, professor and chair of surgery at UC Davis Health, and principal investigator.
She “had been working for this day for nearly 25 years.”
In the early 2000s, Professor Farmer and his colleagues demonstrated that fetal surgery reduced the neurological deficits of spina bifida.
Many children in this study “showed improvement but still needed wheelchairs or leg braces.”
Professor Farmer’s long-term goal is to develop a surgical cure – and she has come to believe that the application of stem cells would be the key.
To that end, she recruited Dr. Aijun Wang, professor of surgery and biomedical engineering at UC Davis. His research focuses on the development of tools and technologies that combine molecular, cellular, tissue and biomaterials engineering to promote regeneration and restore function.
Early work with animals
Their early work proved that prenatal surgery combined with mesenchymal stromal cells derived from the human placenta – held in place with a biomaterial scaffold to form a “patch” – helped lambs with spina bifida walk without noticeable disability.
“When the baby sheep who received stem cells were born, they were able to stand at birth and they were able to run almost normally. It was amazing,” Dr. Wang said.
In the next phase of research, a pair of English bulldogs named Darla and Spanky became the first dogs in the world to be successfully treated with surgery and stem cells.
Spina bifida is a common birth defect in this breed, and it often leaves them with little function in their hindquarters.
On their post-operative re-check at four months old, Darla and Spanky were able to walk, run and play.
In other words, the researchers had demonstrated that their technique was able to prevent the paralysis associated with spina bifida – at least in animals.
The world’s first human trial
Emily and her husband Harry were eager to become parents for the first time when a scan revealed their developing child had spina bifida.
At that time, researchers were recruiting for a human clinical trial. For Emily, “it was a lifeline they couldn’t refuse”.
After screenings, MRIs and interviews, Emily received “the life-changing news” that she had been accepted into the trial. This meant that the couple had to move from Austin, Texas to Sacramento, the Californian capital.
The fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.
The researchers made their clinical-grade stem cells — mesenchymal stem cells — from placental tissue at the Institute for Regenerative Cures at UC Davis Health.
The cells are “known to be among the most promising cell types in regenerative medicine.”
These were used to make the stem cell patch for Emily’s fetal surgery.
“It’s a four-day process to make the stem cell patch,” said Dr. Priya Kumar, a scientist at the Department of Surgery’s Center for Surgical Bioengineering, who leads the team that creates the stem cell patches and delivered to the operating room. bedroom.
“The time we remove the cells, the time we sow on the scaffold and the time we deliver, are all critical.”
A first in medical history
After Emily was placed under general anaesthetic, a small opening was made in her uterus and the fetus floated to the incision point where surgeons exposed the spine and the spina bifida defect.
Surgeons used a microscope to carefully begin the repair.
This involved placing the stem cell patch directly on the exposed spinal cord of the fetus. Fetal surgeons then closed the incision to allow the tissue to grow back.
“The placement of the stem cell patch went smoothly. The mother and the fetus behaved very well! said Professor Farmer.
The team declared the surgery, the first of its kind, a success.
On September 20, 2021, at 35 weeks and five days gestation, Robbie was born by Caesarean section. She weighed 2.5 pounds.
“One of my first fears was not being able to see her, but they brought her to me. I could see his toes wiggle for the first time. It was so reassuring and a bit out of this world,” Emily said.
For Professor Farmer, it was the day she “had long hoped for”, and it came with a sobering surprise: if Robbie had not been treated, it was expected that is born with paralysis of the legs.
“It was very clear from birth that she was kicking her legs and I very clearly remember saying, ‘Oh my God, I think she’s wiggling her toes! ‘” said Professor Farmer, who added that the sighting was unofficial. confirmation, but it was promising.
“It was amazing,” she said. “We kept saying, ‘Do I see this? Is it real?'”
Robbie just celebrated his first birthday. And two other babies have been successfully operated on.
But the team is cautious about drawing conclusions and says there’s still a lot to learn during this safety phase of the trial.
The team will continue to monitor Robbie and the other babies in the trial until they are six years old, with a key checkup at 30 months to see if they are walking and potty training.
“This experience was larger than life and exceeded all expectations. I hope this trial will improve the quality of life for so many future patients,” said Emily. “We are honored to be part of history in the making.”
We have released the first and fourth video documenting Robbie’s research and surgery. The second and third installments can be found here and here.