High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele

Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm(2)) (n = 8), PMSC-ECM (167 K cells/cm(2)) (n = 7), or PMSC-ECM (250-300 K cells/cm(2)) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal curd were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30-70 mu m) were counted manually and density calculated per mm(2) gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5-15]) than ECM alone (6.5 [IQR 4-12.751, p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm(2)) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250-300 K/cm(2)) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. Type of study: Basic science. (C) 2018 Elsevier Inc. All rights reserved.