In utero treatment of myelomeningocele with placental mesenchymal stromal cells — Selection of an optimal cell line in preparation for clinical trials

Autor: Melissa A. Vanover, Jamie E. Anderson, Chelsey Lee, Kaeli J. Yamashiro, Christopher D. Pivetti, Karen Chung, Diana L. Farmer, Laura A. Galganski, Zachary J. Paxton, Lee Lankford, Priyadarsini Kumar, Mennatalla S. Hegazi, Aijun Wang
Rok vydání: 2020
Předmět:
Zdroj: J Pediatr Surg
ISSN: 0022-3468
DOI: 10.1016/j.jpedsurg.2019.09.029
Popis: 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.
Databáze: OpenAIRE
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