Efficacy of Clinical-Grade Human Placental Mesenchymal Stromal Cells in Fetal Ovine Myelomeningocele Repair
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Read the article on jpedsurg.org ↗Article · Jun 2021 · 1 min read
In brief
In brief
Clinical-grade placental mesenchymal stromal cells applied during fetal myelomeningocele repair in sheep restored motor function to near-normal levels, significantly outperforming repair without cells. Strong correlation between spinal neuron density and locomotor outcomes validates this approach for translation to human clinical trials.
Written by the GCMD Library team from the article.
Background
While fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC.
Methods
Thirty-five ovine fetuses underwent MMC defect creation at a median of 76 days gestational age, and defect repair at 101 days gestational age with application of clinical-grade PMSC-ECM (3 × 105 cells/cm2, n=12 fetuses), research-grade PMSC-ECM (3 × 105 cells/cm2, three cell lines with n=6 (Group 1), n=6 (Group 2), and n=3 (Group 3) fetuses, respectively) or ECM without PMSCs (n=8 fetuses). Three normal lambs underwent no surgical interventions. The primary outcome was motor function measured by the Sheep Locomotor Rating scale (SLR, range 0: complete paralysis to 15: normal ambulation) at 24 hours of life. Correlation of lumbar spine large neuron density with SLR was evaluated.
Results
Clinical-grade PMSC-ECM lambs had significantly better motor function than ECM-only lambs (SLR 14.5 vs. 6.5, p=0.04) and were similar to normal lambs (14.5 vs. 15, p=0.2) and research-grade PMSC-ECM lambs (Group 1: 14.5 vs. 15, p=0.63; Group 2: 14.5 vs. 14.5, p=0.86; Group 3: 14.5 vs. 15, p=0.50). Lumbar spine large neuron density was strongly correlated with motor function (r = 0.753, p