The world’s first stem cell treatment of spinobifida performed during fetal surgery

Three babies have been born following the world’s first treatment for spina bifida, which combined surgery with stem cells. This was made possible by a landmark clinical trial at the University of California, Davis.

A one-of-a-kind treatment given while the fetus is still developing in the womb may improve outcomes for children with this birth defect.

The clinical trial, which began in the spring of 2021, is formally known as the “CuRe Trial: Cell Therapy for In utero Repair of Myelomeningocele.” A total of 35 patients will be treated.

The three trial babies born so far will be followed up to 30 months of age by the research team to fully assess the procedure’s safety and effectiveness.

“This clinical trial has the potential to improve the quality of life for so many future patients,” said Emily, a first-time clinical trial participant who traveled from Austin, Texas, to take part. Her daughter Robbie was born last October. “We didn’t know about fissure of the spine before diagnosis. We are very grateful to be a part of it. We are giving our daughter the best chance for a bright future.”

Spina bifida, also known as myelomeningocele, occurs when the tissues of the spine do not fuse properly during the early stages of pregnancy. The birth defect can lead to a range of cognitive, mobility, urinary and bowel problems throughout life. Between 1,500 and 2,000 children are diagnosed with it every year in the United States. It is often diagnosed with ultrasound.

While surgery after birth can reduce some of the effects, surgery before birth can prevent or reduce the severity of fetal spinal damage that worsens during pregnancy.

“I’ve been working toward this day for almost 25 years,” said Diana Farmer, the world’s first female fetal surgeon, professor and chair of surgery at UC Davis Health and the study’s principal investigator.

A path to future treatment

As head of a clinical trial for the treatment of myelomeningocele (MOMS) in the early 2000s, Farmer previously helped prove that operations on the fetus reducing neurological deficits from spina bifida. Many children in this study showed improvement but still required wheelchairs or leg braces.

The farmer hired bioengineer Ayjun Wang specifically to help take this work to the next level. Together, they launched UC Davis’ Surgical Bioengineering Laboratory to find ways to use stem cells and bioengineering to improve surgical efficiency and improve outcomes. Farmer also opened the UC Davis Center for Fetal Care and Treatment with fetal surgeon Shinjiro Hirose and the UC Davis Center for Pediatric Surgery several years ago.

Farmer, Wang and their research team have been working on their new approach to using stem cells in fetal surgery for more than 10 years. During this time, animal modeling showed that it was able to prevent paralysis associated with spina bifida.

Stem cells are believed to regenerate and repair damaged spinal cord tissue beyond what surgery alone can achieve.

Previous work by Farmer and Wang showed that prenatal surgery combined with human placental mesenchymal stromal cells held in place by a biomaterial scaffold to form a “tray” helped lambs with spina bifida to walk without noticeable disability.

“When the sheep that received the stem cells were born, they were able to stand at birth and run almost normally. It was amazing,” Wang said.

As the team perfected their surgery and stem cell technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida.

A pair of English bulldogs named Darla and Spanky were the first dogs in the world to be successfully treated with surgery and stem cells. Spina bifida, common congenital defect in this breed, often leaves them with little function in their hind limbs.

After rechecking after surgery at 4 months, Darla and Spanky were able to walk, run and play.

The world’s first human trial

When Emily and her husband Harry found out they were going to be parents for the first time, they didn’t expect any complications during the pregnancy. But the day Emily found out her baby had spina bifida was the first time she heard about the CuRe trial.

For Emily, it was a lifeline they couldn’t let go of.

Participating in the trial will mean she will need to temporarily move to Sacramento for fetal surgery and then for weekly follow-up visits during her pregnancy.

After tests, an MRI and an interview, Emily received the life-changing news that she had been admitted to court. Her fetal surgery was scheduled for July 12, 2021 at 25 weeks and five days.

Farmer and Wang’s team produces clinical-grade stem cells –mesenchymal stem cells— from placental tissue at UC Davis’ Institute for Regenerative Medicine. Stem cells are known to be one of the most promising cell types in regenerative medicine.

The laboratory is a Good Manufacturing Practice (GMP) laboratory for safe human use. It was here that they made the stem cell patch for the operation on Emily’s fetus.

“It takes four days to create a stem cell patch,” said Priya Kumar, a scientist in the Department of Surgery’s Center for Surgical Bioengineering who leads the team that creates the stem cell patches and delivers them to the operating room. . “The time we’re pulling cellsthe time we sow on the scaffold and the time we deliver are all very important.”

The first in the history of medicine

During Emily’s historic procedure, the operation and preparation team of 40 people performed a careful dance for which they had been preparing for a long time.

After Emily was put under general anesthesia, a small opening was made in her uterus and they lifted the fetus up to this point of incision so that its spine and spina bifida defect could be exposed. Surgeons carefully began the repair with the help of a microscope.

Then came the moment of truth: a stem cell patch was placed directly on the exposed fetal spinal cord. Fetal surgeons then closed the incision to allow the tissue to regenerate.

“The stem cell patch placement went smoothly. Mother and fetus did great!” – said the farmer.

The team is announced as the first of its kind surgical intervention success

Delivery day

On September 20, 2021, at 35 weeks and five days’ gestation, Robbie was born by caesarean section weighing 5 pounds 10 ounces and measuring 19 inches.

“One of my first fears was that I wouldn’t be able to see her, but they brought her to me. I saw her toes move for the first time. It was so reassuring and a little out of this world,” Emily said.

For Farmer, this day is something she’s been hoping for for a long time, and it brought some surprises. Had Robbie not been treated, she was expected to be born with paralysis of the legs.

“The moment she was born it was very clear that she was kicking and I remember very clearly saying, ‘Oh my God, I think she’s wiggling her toes!’ — said Farmer, who noted that the sighting was not official confirmation, but it was promising. “It was amazing. We kept saying, “Can I see it? Is it real?”

Both mother and child are at home, they are doing well. Robbie just celebrated her first birthday.

The CuRe team is cautious about drawing conclusions, saying there is still much to learn at this stage of safety testing. The team will continue to follow Robbie and the other babies in the trial until they are 6 years old, with a follow-up at 30 months to see if they are walking and potty trained.

“This experience was larger than life and exceeded all expectations. I hope this trial will improve the quality of life for many future patients,” said Emily. “We are honored to be a part of history in the making.”