UC Davis fetal surgeon Dr. Diana Farmer has been at the forefront of treating spina bifida in infants while they are still in their mother’s womb. Now, Dr. Farmer and her colleagues have used a large animal model system to study the use of stem cells to improve the clinical outcomes of children who undergo these types of in utero procedures.
Spina bifida is a congenital birth defect that results from abnormal development of the spinal cord. During development, the spinal cord, which beings as a tube (the neural tube), is open at both ends, and these ends eventually close. However, if the posterior opening to the neural tube does not close properly, then the developing spinal cord will have severe structural defects. These structural defects adversely affect the nerves that issue from the spinal cord and spinal bifida can cause lifelong cognitive, urological, musculoskeletal and motor disabilities.
Dr. Farmer’s chief collaborator was another UC Davis science named Aijun Wang, who serves as the co-director of the UC Davis Surgical Bioengineering Laboratory.
“Prenatal surgery revolutionized spina bifida treatment by improving brain development, but it didn’t benefit motor function as much as we hoped,” said Farmer, who serves as chair of the UC Davis Department of Surgery and is the senior author of this study, which was published online in the journal Stem Cells Translational Medicine.
“We now think that when it’s augmented with stem cells, fetal surgery could actually be a cure,” said Wang.
Years ago, Farmer and her colleagues showed in an extensive clinical trial called the Management of Myelomeningocele Study (MOMS) that babies who were diagnosed with spina bifida and were eligible for in utero surgery had better outcomes that babies who underwent surgery after they were born. Babies with spina bifida who were operated on in utero had a better chance of walking, and not needing a shunt to deal with the pressure problems in the brain that some children with spina bifida experience (see N. Scott Adzick, et al., New England Journal of Medicine 2011;364(11):993-1004). Even with this study, the majority of the babies who were treated with in utero surgery were still unable to walk. To improve a baby’s chances of walking, Farmer and her collaborators turned to stem cell treatments.
Farmer and Wang combined fetal surgery with a the transplantation of stem cells from human placentas to improve neurological capabilities of babies born with spina bifida. In children, spina bifida can range from barely noticeable to rather severe. Myelomeningocele is the most common and, unfortunately, the most disabling form of spina bifida. In babies with myelomeningocele, the spinal emerges through the back and usually pulls brain tissue into the spinal column, which causes cerebrospinal fluid to fill the interior of the brain. Therefore, such patients require permanent shunts in their brains in order to drain the extra cerebrospinal fluid.
In this study, lambs with myelomeningocele were operated on in utero in order to return exposed spinal cord tissue into the vertebral column. Then human placenta-derived mesenchymal stromal cells (PMSCs), which have demonstrated neuroprotective qualities (see Yun HM, et al., Cell Death Dis. 2013;4:e958), were embedded in hydrogel and applied to the site of the lesion. A scaffold was placed on top to hold the hydrogel in place, and the surgical opening was closed.
Six of the animals that received the stem cell treatment were able to walk without noticeable disability within a few hours following birth. However, the six control animals that received only the hydrogel and scaffold were unable to stand.
“We have taken a very important step in expanding what MOMS started,” said Wang. “Next we need to confirm the safety of the approach and determine optimal dosing.”
Farmer and Wang will continue their efforts with funding from the California Institute for Regenerative Medicine. With additional evaluation and FDA approval, the new therapy could be tested in human clinical trials.
“Fetal surgery provided hope that most children with spina bifida would be able to live without shunts,” Farmer said. “Now, we need to complete that process and find out if they can also live without wheelchairs.”