Fetal surgical repair with placenta-derived mesenchymal stromal cell engineered patch in a rodent model of myelomeningocele.

Public Summary Purpose: Myelomeningocele (MMC), or spina bifida, is a neural tube defect that leads to paralysis, bladder incontinence and bowel dysfunction due to spinal cord injury. Fetal intervention provides coverage of the spinal cord to prevent further intrauterine damage; however it cannot reverse previously acquired damage. Our laboratory has demonstrated that placenta derived mesenchymal stromal cells (PMSCs) have the ability to help protect neurons and rescue motor function in a sheep model of MMC. The goal of this study was to determine the feasibility of fetal surgical repair of MMC in a rodent model using human PMSCs. Methods: Stem cells were isolated from second trimester placenta and seeded onto tissue patches (extracellular matrix). Fetal rodents with MMC underwent surgical repair using the stem cells and tissue patch. We tested various densities of stem cells. Fetal rodents were then delivered three days later. We measured the spinal cord and determined the number of apoptotic, or dead, cells. Results: 121 pups underwent MMC repair and 103 (85.1%) survived to delivery. Pups treated with the stem cells and tissue patch at all seeding densities resulted in significantly less cord compression compared to pups repaired with tissue patch only and unrepaired controls. Pups treated with the highest seeding density of PMSCs had significantly lower apoptotic cells compared to the tissue patch only. Conclusion: Surgical repair of MMC with stem cells on a tissue patch is feasible with a survival rate of 85.1%. Fetal rodents repaired with stem cells and a tissue patch have significantly less cord deformity and decreased evidence of apoptosis compared to the tissue patch only controls. This indicates that PMSCs may be capable of enhancing fetal wound healing and remodeling of the MMC spinal cord.