Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele

Purpose: The purpose of this study was to investigate the effects of placental mesenchymal stromal cells (PMSCs) seeded on a clinical grade porcine small intestinal submucosa (SIS)-derived extracellular matrix (ECM) on hindlimb motor function in an ovine fetal repair model of myelomeningocele (MMC). Methods: MMC defects were surgically created in 21 fetuses at median gestational age 78 (range 76-83) days. Fetuses were randomly assigned to repair 25 days later with ECMonly or PMSC-ECM. Surviving fetuses were delivered at term. Motor function was evaluated using the Sheep Locomotor Rating (SLR) scale (0-15). Histologic analysis of the spinal cord (SC) was completed. Results: Fetal viability was 71%. 5 of 8 (63%) lambs repaired with PMSC-ECM ambulated independently versus only 1 of 6 (17%) repaired with ECM only (p = 0.04, chi(2) test). SLR scores and large neuron densities were higher in the PMSC-ECM group. The cross-sectional areas of the SC and the gray matter were equally preserved. Conclusions: Fetal repair of MMC with PMSCs seeded on SIS-ECM improves hindlimb motor function in lambs. Using ECM helps to preserve the architecture of the SC, but adding PMSCs improves the lamb's ability to walk and increases large neuron density. Clinical studies are needed to show benefits in humans. Levels of evidence/type of study: Basic Science. (C) 2017 Elsevier Inc. All rights reserved.