High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele

Melissa Vanover, Christopher Pivetti, Lee Lankford, Priyadarsini Kumar, Laura Galganski, Sandra Kabagambe, Benjamin Keller, James Becker, Y. Julia Chen, Karen Chung, Chelsey Lee, Zachary Paxton, Bailey Deal, Laura Goodman, Jamie Anderson, Guy Jensen, Aijun Wang, Diana L Farmer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm2) (n = 8), PMSC-ECM (167 K cells/cm2) (n = 7), or PMSC-ECM (250–300 K cells/cm2) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30–70 μm) were counted manually and density calculated per mm2 gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5–15]) than ECM alone (6.5 [IQR 4–12.75], p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm2) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250–300 K/cm2) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. Type of study: Basic science. Level of evidence: N/A

Original languageEnglish (US)
JournalJournal of Pediatric Surgery
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Meningomyelocele
Mesenchymal Stromal Cells
Extracellular Matrix
Sheep
Spinal Cord
Neurons
Random Allocation
Fetus

Keywords

  • Fetal surgery
  • Mesenchymal stromal cell
  • Myelomeningocele
  • Neuroprotection
  • Placenta
  • Tissue engineering

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele. / Vanover, Melissa; Pivetti, Christopher; Lankford, Lee; Kumar, Priyadarsini; Galganski, Laura; Kabagambe, Sandra; Keller, Benjamin; Becker, James; Chen, Y. Julia; Chung, Karen; Lee, Chelsey; Paxton, Zachary; Deal, Bailey; Goodman, Laura; Anderson, Jamie; Jensen, Guy; Wang, Aijun; Farmer, Diana L.

In: Journal of Pediatric Surgery, 01.01.2018.

Research output: Contribution to journalArticle

Vanover, Melissa ; Pivetti, Christopher ; Lankford, Lee ; Kumar, Priyadarsini ; Galganski, Laura ; Kabagambe, Sandra ; Keller, Benjamin ; Becker, James ; Chen, Y. Julia ; Chung, Karen ; Lee, Chelsey ; Paxton, Zachary ; Deal, Bailey ; Goodman, Laura ; Anderson, Jamie ; Jensen, Guy ; Wang, Aijun ; Farmer, Diana L. / High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele. In: Journal of Pediatric Surgery. 2018.
@article{7d137387f1334617b9b5f9ebdf6e32e8,
title = "High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele",
abstract = "Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm2) (n = 8), PMSC-ECM (167 K cells/cm2) (n = 7), or PMSC-ECM (250–300 K cells/cm2) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30–70 μm) were counted manually and density calculated per mm2 gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5–15]) than ECM alone (6.5 [IQR 4–12.75], p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm2) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250–300 K/cm2) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. Type of study: Basic science. Level of evidence: N/A",
keywords = "Fetal surgery, Mesenchymal stromal cell, Myelomeningocele, Neuroprotection, Placenta, Tissue engineering",
author = "Melissa Vanover and Christopher Pivetti and Lee Lankford and Priyadarsini Kumar and Laura Galganski and Sandra Kabagambe and Benjamin Keller and James Becker and Chen, {Y. Julia} and Karen Chung and Chelsey Lee and Zachary Paxton and Bailey Deal and Laura Goodman and Jamie Anderson and Guy Jensen and Aijun Wang and Farmer, {Diana L}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jpedsurg.2018.10.032",
language = "English (US)",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele

AU - Vanover, Melissa

AU - Pivetti, Christopher

AU - Lankford, Lee

AU - Kumar, Priyadarsini

AU - Galganski, Laura

AU - Kabagambe, Sandra

AU - Keller, Benjamin

AU - Becker, James

AU - Chen, Y. Julia

AU - Chung, Karen

AU - Lee, Chelsey

AU - Paxton, Zachary

AU - Deal, Bailey

AU - Goodman, Laura

AU - Anderson, Jamie

AU - Jensen, Guy

AU - Wang, Aijun

AU - Farmer, Diana L

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm2) (n = 8), PMSC-ECM (167 K cells/cm2) (n = 7), or PMSC-ECM (250–300 K cells/cm2) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30–70 μm) were counted manually and density calculated per mm2 gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5–15]) than ECM alone (6.5 [IQR 4–12.75], p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm2) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250–300 K/cm2) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. Type of study: Basic science. Level of evidence: N/A

AB - Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm2) (n = 8), PMSC-ECM (167 K cells/cm2) (n = 7), or PMSC-ECM (250–300 K cells/cm2) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30–70 μm) were counted manually and density calculated per mm2 gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5–15]) than ECM alone (6.5 [IQR 4–12.75], p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm2) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250–300 K/cm2) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. Type of study: Basic science. Level of evidence: N/A

KW - Fetal surgery

KW - Mesenchymal stromal cell

KW - Myelomeningocele

KW - Neuroprotection

KW - Placenta

KW - Tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=85055477797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055477797&partnerID=8YFLogxK

U2 - 10.1016/j.jpedsurg.2018.10.032

DO - 10.1016/j.jpedsurg.2018.10.032

M3 - Article

C2 - 30529115

AN - SCOPUS:85055477797

JO - Journal of Pediatric Surgery

JF - Journal of Pediatric Surgery

SN - 0022-3468

ER -