Fetal tissue engineering in an ovine model

描述(申请人提供)：在第一个项目中，我们打算改进用于在已建立的绵羊模型中创建组织工程补片的技术，用于预防新生儿先天性横隔膜修复后的胃肠再突出。我们还计划调查胚胎间充质细胞在植入前的体外机械预适应是否会导致改善结果。在第二个项目中，我们将在一大群绵羊身上研究神经干细胞修复胎儿脊髓脊膜膨出(MMC)的神经学、胃肠道和泌尿学结果。在分娩前大约30天(怀孕110-115天)，通过手术制造的MMC的胎儿羔羊将接受Gortex(Tm)贴片缝合，并将神经干细胞种植到可生物降解的支架上。适当的对照动物也将同时进行研究。运动、感觉和尿动力学测试将在出生后72小时内进行。将对脊髓和肛门括约肌进行组织病理学分析，以评估其正常发育。在最后一个项目中，我们将对人和绵羊羊水间充质细胞的免疫学特性和分化潜能进行表征。

DESCRIPTION (provided by applicant): 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.