Validation of the ovine fetus as an experimental model for the human myelomeningocele defect

Abstract

PURPOSE: To produce a myelomeningocele-like human defect in the ovine fetus and validate this experimental model in our population. METHODS: A prospective study on 12 pregnant sheep of a crossed Hampshire/Down breed where a spinal defect was surgically created between Day 75 and Day 77 after conception. The technique consisted of a hysterotomy with exposure of fetal hind limbs and tail up to the mid spine. Fetal skin, paravertebral muscles, and 4 posterior spinal arches were excised, exposing the spinal cord. Duramater was opened and the medulla was incised until the medullar canal. Animals were euthanized at 139 days of gestation for fetal evaluation. The central nervous system was submitted to post-mortem magnetic resonance imaging (MRI) and the spine was submitted to pathological examination. RESULTS: The defect was created in 13 fetuses and 5 survived. Mean gestational age at necropsy was 121.6 days (varying from 93 to 145 days). Macroscopically, the defect was present in 4 cases. Microscopy revealed a flattened medulla with disappearance of the medullar canal and disruption of normal medullar architecture with neuronal apoptosis and/or fusion of the piamater and duramater. The MRI showed herniation of the cerebellum into the cervical canal and syringomyelia. CONCLUSIONS: The surgically produced defect mimics the defect found in the human fetus, including the Arnold-Chiari malformation. Post-mortem MRI was used for the first time in our study and proved an excellent alternative for demonstrating the cerebellar herniation. We standardized the technique for creating the defect in our population.

Simplified correction of a meningomyelocele-like defect in the ovine fetus

“…Toward this goal, our group previously developed a simplified technique using a cellulose biomatrix as an interface material in a rabbit model 14 . In the present study, we extend these studies by testing the efficacy of this new technique in an ovine model 15 .…”

“…These authors observed that lambs developed lumbar cystic sacs with abnormal spinal cord tissue on the dorsal aspect and histology revealed loss of neural tissue, disruption of neural bundles and areas of cord necrosis in the exposed segments, strikingly similar to that seen in human MMC. Since then many other researchers 6,15,17,18 have been using and accepting this model for MMC studies. Subsequent sheep studies have shown that if a lumbar myelotomy was added during the creation of the defect also hindbrain herniation, similar to humans would occur.…”

“…A hysterotomy was performed to expose the fetal lumbar spine. A spinal defect was created at 75 days gestation (range 74-78) using a modified technique from the initially proposed by Meuli et al 16 and modified by Paek et al 17 , that we have previously tested 15 . Briefly, the skin and paraspinal muscles overlying the lumbar portion of the fetal spine were removed to expose a 3 x 2 cm area.…”

Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta)

“…in rabbits, Meuli et al 9 in sheep, Pedreira et al 10 in ovine fetuses and Michjeda 11 in non human primates Macaca mulatta; creating intrauterine surgical models to reproduce different diseases and perform its correction. Also George and Fuh 12 , describe the use of non-human primates (Macaca mulatta), as models for the surgical correction of diseases for the neural tube.…”

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results

“…However, ovines are excellent animal model for translational medicine because the body scores close to humans and as production animal, a suitable specie for housekeeping and management [7][8][9][10] .…”