A baby girl, Robbie, is the first human to receive experimental surgery involving the placement of a stem cell patch that repairs and restores damaged tissue to the spine.
The pioneering spina bifida surgery, involving a team of 40 from the University of California Davis, occurred when Robbie was still developing in her mother’s womb.
As the researchers from the University of California Davis describe it, this novel fetal surgery “could change the life of a developing baby with spina bifida, who otherwise could be born paralysed from the waist down”.
Prior to Robbie’s surgery, the treatment had only been trialled on sheep and dogs.
Robbie was kicking her legs soon after being 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 don’t form properly.
The neural tube is the structure in a developing embryo that eventually becomes the baby’s brain, spinal cord and the tissues that enclose them.
The defect can lead to a range of lifelong cognitive, mobility, urinary and bowel disabilities. Some children spend their lives in wheelchairs.
Surgery performed after birth can help reduce some of the effects – while surgery before birth can prevent or lessen the severity of the fetus’s spinal damage, which worsens over the course of pregnancy.
A long time coming
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’d been “working toward this day for almost 25 years”.
In the early 2000s, Professor Farmer and colleagues demonstrated that fetal surgery reduced neurological deficits from spina bifida.
Many children in that study “showed improvement but still required wheelchairs or leg braces”.
Professor Farmer’s long-term goal is to develop a surgical cure – and she came to believe the application of stem cells would be key.
To that end she recruited Dr Aijun Wang, Professor of Surgery and of Biomedical Engineering at UC Davis. His research focuses on developing tools and technologies that combine molecular, cellular, tissue and biomaterial engineering to promote regeneration and restore function.
Early work with animals
Their early work proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells – 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 around almost normally. It was amazing,” Dr Wang said.
In the next phase of the research, a pair of English bulldogs named Darla and Spanky became the world’s first dogs to be successfully treated with surgery and stem cells.
Spina bifida is a common birth defect in this breed, and it frequently leaves them with little function in their hindquarters.
By their post-surgery re-check at four months old, Darla and Spanky were able to walk, run and play.
In other words, the researchers had demonstrated their technique was capable of preventing the paralysis associated with spina bifida – at least in animals.
The world’s first human trial
Emily and her husband Harry were looking forward to becoming first-time parents when a scan revealed that their developing child had spina bifida.
At that time, the researchers were recruiting for a human clinical trial. For Emily, “it was a lifeline that they couldn’t refuse”.
After screenings, MRI scans and interviews, Emily received “the life-changing news” that she was accepted into the trial. It meant the couple needed 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 manufactured their clinical grade stem cells – mesenchymal stem cells – from placental tissue in the UC Davis Health’s Institute for Regenerative Cures.
The cells are “known to be among the most promising type of cells in regenerative medicine”.
These were used to they 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, the scientist at the Center for Surgical Bioengineering in the Department of Surgery, who leads the team that creates the stem cell patches and delivers them to the operating room.
“The time we pull out the cells, the time we seed on the scaffold, and the time we deliver, is all critical.”
A first in medical history
After Emily was placed under general anesthetic, a small opening was made in her uterus and the fetus was floated up to the incision point where the surgeons exposed the spine and the spina bifida defect.
The surgeons used a microscope to carefully begin the repair.
This involved placing the stem cell patch directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate.
“The placement of the stem cell patch went off without a hitch. Mother and fetus did great!” Professor Farmer said.
The team declared the first-of-its-kind surgery a success.
Delivery day
On Sept. 20, 2021, at 35 weeks and five days gestation, Robbie was born via C-section. She weighed 2.5 kilos.
“One of my first fears was that I wouldn’t be able to see her, but they brought her over to me. I got to see her toes wiggle for the first time. It was so reassuring and a little bit out of this world,” Emily said.
For Professor Farmer, this was the day she “had long hoped for”, and it came with a sobering surprise: if Robbie had remained untreated, she was expected to be born with leg paralysis.
“It was very clear the minute she was born that she was kicking her legs and I remember very clearly saying, ‘Oh my God, I think she’s wiggling her toes!'” said Professor Farmer, who added that the observation was not an official confirmation, but it was promising.
“It was amazing,” she said. “We kept saying, ‘Am I seeing that? Is that real?'”
Robbie just celebrated her first birthday. And two other babies have been successfully operated on.
But the team is cautious about drawing conclusions and says a lot is still to be learned 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 happening at 30 months to see if they are walking and potty training.
“This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come,” Emily said. “We are honored to be part of history in the making.”
We’ve published the first and fourth video that documents the research and Robbie’s surgery. The second and third instalments can be found here and here.
