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 language | English (US) |
|---|---|
| Journal | Journal of pediatric surgery |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
Fingerprint
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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85074385095&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074385095&partnerID=8YFLogxK
U2 - 10.1016/j.jpedsurg.2019.09.029
DO - 10.1016/j.jpedsurg.2019.09.029
M3 - Article
C2 - 31672407
AN - SCOPUS:85074385095
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
SN - 0022-3468
ER -