Bulldog puppy Darla at a follow-up appointment
A University of California–Davis veterinary and medical school team recently tested an experimental spina bifida stem cell therapy on two English Bulldogs born with the condition. The treatment, which uses both surgery and stem cell implantation, aims to restore lower limb function. Ultimately, the researchers would like to extend the promising therapy to humans.
What is spina bifida?
Spina bifida affects 1,500 -2,000 babies born in the US annually. Spina bifida is a neural tube defect that occurs when spinal tissue fails to develop properly. Lower limb weakness, incontinence, hydrocephalus and a tethered spinal cord characterize the condition. Myelomeningocele is one of the most common complications of spina bifida. It causes the spinal cord to protrude from the lower back, and draws brain tissue into the spinal column. Cerebrospinal fluid becomes trapped in the brain, and creates cognitive impairments in affected individuals. Although doctors can detect spina bifida in utero, post-natal treatment normally consists of implanting a shunt to allow cerebrospinal fluid to escape the skull and reduce pressure on the brain.
Many spina bifida patients can walk only with assistance, or use a wheelchair. The condition does not improve over time, and mobility issues remain a lifelong challenge for spina bifida patients. Spina bifida occurs spontaneously in both humans and animals. Because there is no effective treatment for the condition, veterinarians normally recommend destroying affected animals upon diagnosis.
Combining surgery and stem cell therapy
The UC-Davis veterinary research team modified a pre-natal surgical intervention developed by UC-Davis fetal surgeon Diana Farmer. Farmer and her team have pioneered both pre-natal surgical interventions and stem cell treatments for patients with spina bifida. Farmer’s earlier work aimed to improve brain development in babies born with the condition through prenatal corrective surgery. While Farmer’s work successfully improved brain function and eliminated the need for permanent shunts, it did not improve patients’ mobility issues.
Farmer theorized that combining her pre-natal corrective surgery with stem cells could produce a better mobility outcomes. Using six fetal lambs with the condition, Farmer surgically repaired the myelomeningocele, by placing the exposed spinal cord into the spinal canal. She then applied human placenta-derived mesenchymal stromal cells (PMSC) suspended in a hydrogel to the site of the spinal lesion. To ensure good contact with the lesion, Farmer added a protective scaffold before closing the surgical site.
Six fetal control animals with the condition received the surgery, scaffolding and hydrogel without stem cells. Just hours after birth, the six lambs that received stem cells walked with no noticeable difficulty. The six control animals showed no detectable improvement in their mobility at birth.
Applying pre-natal stem cell technique following birth
Dr. Beverly Sturges, a UC-Davis veterinary neurosurgeon wanted to test Farmer’s technique on puppies with the condition. Since veterinarians do not screen dogs for birth defects, Sturges wanted to attempt the repair on post-natal animals. Sturges got her chance when a local bulldog rescue group transferred two 10-week-old siblings with spina bifida to the university’s veterinary hospital.
Dr. Sturges used canine PMSCs and Farmer’s technique to treat the puppies. Six weeks after the surgery, both puppies could walk and run, and showed good hind limb control. They also had a noticeably improved range of motion in their hindquarters. Sturges’ team has not noted a positive effect on the dogs’ incontinence. The team will continue to monitor the dogs for signs of improved bladder and bowel control over time.
Dr. Farmer and her team hope their promising pre-natal and post-natal animal results will persuade the US Food and Drug Administration to authorize human clinical trials for the therapy. If they can demonstrate similar success in human clinical trials, they believe their work could be a functional cure for spina bifida. Like Farmer, Sturges believes that the treatment could effectively eliminate spina bifida in dogs and eliminate the standard practice of euthanizing animals with the condition.
Application of the UC Davis research demonstrates the positive potential of stem cells in the development of new therapies for prenatal patients. If you would like more information about stem cells and the work of the National Dental Pulp Laboratory, please contact us here, or call us at (774) 843-2984.
