In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells — Selection of an Optimal Cell Line in Preparation for Clinical Trials
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In brief
In brief
Ovine model study evaluating three human placental mesenchymal stromal cell lines for in utero myelomeningocele repair. Lines A and B demonstrated superior neuroprotection in vitro and achieved 71-83% ambulation rates versus 20% without cells, validating in vitro assays for clinical cell line selection.
Written by the GCMD Library team from the article.
Background
We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model.
Methods
PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model. In vivo, myelomeningocele defects were created in 28 fetuses and repaired with PMSCs at 3 × 105 cells/cm2 of scaffold from Line A (n = 6), Line B (n = 7) and Line C (n = 5) and compared to no PMSCs (n = 10). Ambulation was scored as ≥13 on the Sheep Locomotor Rating Scale.
Results
In vitro, Line A and B had higher neuroprotective capability than no PMSCs (1.7 and 1.8 respectively vs 1, p = 0.02, ANOVA). In vivo, Line A and B had higher large neuron densities than no PMSCs (25.2 and 27.9 respectively vs 4.8, p = 0.03, ANOVA). Line C did not have higher neuroprotection or larger neuron density than no PMSCs. In vivo, Line A and B had ambulation rates of 83% and 71%, respectively, compared to 60% with Line C and 20% with no PMSCs.
Conclusion
The in vitro neuroprotection assay will facilitate selection of optimal PMSC lines for clinical use.
Level of evidence
n/a.
Type of study
Basic science.