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

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

Research output: Contribution to journalArticle

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 × 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.

Original languageEnglish (US)
JournalJournal of pediatric surgery
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Meningomyelocele
Mesenchymal Stromal Cells
Clinical Trials
Walking
Cell Line
Sheep
Analysis of Variance
Neurons
Placenta
Fetus
Apoptosis
Pregnancy
In Vitro Techniques
Neuroprotection

Keywords

  • Fetal surgery
  • Mesenchymal stromal cell
  • Myelomeningocele
  • Potency
  • Spina bifida

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells — Selection of an Optimal Cell Line in Preparation for Clinical Trials. / Galganski, Laura A.; Kumar, Priyadarsini; Vanover, Melissa A.; Pivetti, Christopher D.; Anderson, Jamie E.; Lankford, Lee; Paxton, Zachary J.; Chung, Karen; Lee, Chelsey; Hegazi, Mennatalla S.; Yamashiro, Kaeli J.; Wang, Aijun; Farmer, Diana L.

In: Journal of pediatric surgery, 01.01.2019.

Research output: Contribution to journalArticle

Galganski, Laura A. ; Kumar, Priyadarsini ; Vanover, Melissa A. ; Pivetti, Christopher D. ; Anderson, Jamie E. ; Lankford, Lee ; Paxton, Zachary J. ; Chung, Karen ; Lee, Chelsey ; Hegazi, Mennatalla S. ; Yamashiro, Kaeli J. ; Wang, Aijun ; Farmer, Diana L. / In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells — Selection of an Optimal Cell Line in Preparation for Clinical Trials. In: Journal of pediatric surgery. 2019.
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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 × 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.",
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T1 - In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells — Selection of an Optimal Cell Line in Preparation for Clinical Trials

AU - Galganski, Laura A.

AU - Kumar, Priyadarsini

AU - Vanover, Melissa A.

AU - Pivetti, Christopher D.

AU - Anderson, Jamie E.

AU - Lankford, Lee

AU - Paxton, Zachary J.

AU - Chung, Karen

AU - Lee, Chelsey

AU - Hegazi, Mennatalla S.

AU - Yamashiro, Kaeli J.

AU - Wang, Aijun

AU - Farmer, Diana L.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Fetal surgery

KW - Mesenchymal stromal cell

KW - Myelomeningocele

KW - Potency

KW - Spina bifida

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