In the first project, we intend to refine the techniques for creating tissue engineered patches used to prevent gastrointestinal re-herniation after neonatal congenital diaphragmatic repair in an established ovine model. We also plan to investigate whether in vitro mechanical preconditioning of fetal mesenchymal cells prior to implantation leads to improved outcomes. In the second project, we will investigate the neurologic, gastrointestinal, and urologic outcomes of fetal myelomeningocele (MMC) repair with neural stem cells in a large series of sheep. Approximately 30 days before term (110-115 days gestation), fetal lambs with a surgically created MMC will undergo Gortex(tm) patch closure plus the delivery of neural stem cells seeded onto a biodegradable scaffold. The appropriate control animals will also be studied in parallel. Motor, sensory, and urodynamic testing will occur within 72 hours of birth. The spinal cord and anal sphincter muscles will be analyzed histopathologically to assess for normal development. In the last project, we will characterize the immunologic properties and differentiation potential of human and ovine amniotic fluid mesenchymal cells. ? ?
