In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells - Selection of an Optimal Cell Line in Preparation for Clinical Trials

Overview

Journal J Pediatr Surg

Specialties General Surgery
Pediatrics

Date 2019 Nov 2

PMID 31672407

Citations 16

Authors

Laura A Galganski

Priyadarsini Kumar

Melissa A Vanover

Christopher D Pivetti

Jamie E Anderson

Lee Lankford

Zachary J Paxton

Karen Chung

Chelsey Lee

Mennatalla S Hegazi

Kaeli J Yamashiro

Aijun Wang

Diana L Farmer

Affiliations

Soon will be listed here.

Abstract

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 × 10 cells/cm 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.

Citing Articles

Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair.

Athiel Y, Cariot L, Jouannic J, Maillet C, Mauffre V, Adam C Stem Cell Res Ther. 2024; 15(1):444.

PMID: 39568021 PMC: 11580231. DOI: 10.1186/s13287-024-03991-y.

The Placenta as a Source of Human Material for Neuronal Repair.

Dallatana A, Cremonesi L, Pezzini F, Fontana G, Innamorati G, Giacomello L Biomedicines. 2024; 12(7).

PMID: 39062139 PMC: 11275125. DOI: 10.3390/biomedicines12071567.

Biodistribution of allogenic umbilical cord-derived mesenchymal stromal cells after fetal repair of myelomeningocele in an ovine model.

Athiel Y, Nasone J, Arakelian L, Faivre L, Dugas A, Jouannic J Stem Cell Res Ther. 2022; 13(1):300.

PMID: 35841029 PMC: 9284777. DOI: 10.1186/s13287-022-02991-0.

Dural substitutes for spina bifida repair: past, present, and future.

Miyabe M, Murphy K, Oria M, Duru S, Lin C, Peiro J Childs Nerv Syst. 2022; 38(5):873-891.

PMID: 35378616 PMC: 9968456. DOI: 10.1007/s00381-022-05486-8.

Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells.

Stokes S, Kabagambe S, Lee C, Wang A, Farmer D, Kumar P J Surg Res. 2022; 273:201-210.

PMID: 35093836 PMC: 9396930. DOI: 10.1016/j.jss.2021.12.039.

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