Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele

Sandra Kabagambe, Benjamin Keller, James Becker, Laura Goodman, Christopher Pivetti, Lee Lankford, Karen Chung, Chelsey Lee, Y. Julia Chen, Priyadarsini Kumar, Melissa Vanover, Aijun Wang, Diana L Farmer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: The purpose of this study was to investigate the effects of placental mesenchymal stromal cells (PMSCs) seeded on a clinical grade porcine small intestinal submucosa (SIS)-derived extracellular matrix (ECM) on hindlimb motor function in an ovine fetal repair model of myelomeningocele (MMC). Methods: MMC defects were surgically created in 21 fetuses at median gestational age 78 (range 76-83) days. Fetuses were randomly assigned to repair 25. days later with ECM only or PMSC-ECM. Surviving fetuses were delivered at term. Motor function was evaluated using the Sheep Locomotor Rating (SLR) scale (0-15). Histologic analysis of the spinal cord (SC) was completed. Results: Fetal viability was 71%. 5 of 8 (63%) lambs repaired with PMSC-ECM ambulated independently versus only 1 of 6 (17%) repaired with ECM only (p=0.04, χ2 test). SLR scores and large neuron densities were higher in the PMSC-ECM group. The cross-sectional areas of the SC and the gray matter were equally preserved. Conclusions: Fetal repair of MMC with PMSCs seeded on SIS-ECM improves hindlimb motor function in lambs. Using ECM helps to preserve the architecture of the SC, but adding PMSCs improves the lamb's ability to walk and increases large neuron density. Clinical studies are needed to show benefits in humans. Levels of evidence/type of study: Basic Science.

Original languageEnglish (US)
JournalJournal of Pediatric Surgery
DOIs
StateAccepted/In press - 2017

Fingerprint

Meningomyelocele
Mesenchymal Stromal Cells
Walking
Extracellular Matrix
Sheep
Spinal Cord
Fetus
Hindlimb
Fetal Viability
Neurons
Gestational Age
Swine

Keywords

  • Fetal surgery
  • Mesenchymal stromal cells
  • Myelomeningocele
  • Placenta
  • Tissue engineering

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele. / Kabagambe, Sandra; Keller, Benjamin; Becker, James; Goodman, Laura; Pivetti, Christopher; Lankford, Lee; Chung, Karen; Lee, Chelsey; Chen, Y. Julia; Kumar, Priyadarsini; Vanover, Melissa; Wang, Aijun; Farmer, Diana L.

In: Journal of Pediatric Surgery, 2017.

Research output: Contribution to journalArticle

Kabagambe, Sandra ; Keller, Benjamin ; Becker, James ; Goodman, Laura ; Pivetti, Christopher ; Lankford, Lee ; Chung, Karen ; Lee, Chelsey ; Chen, Y. Julia ; Kumar, Priyadarsini ; Vanover, Melissa ; Wang, Aijun ; Farmer, Diana L. / Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele. In: Journal of Pediatric Surgery. 2017.
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AU - Kabagambe, Sandra

AU - Keller, Benjamin

AU - Becker, James

AU - Goodman, Laura

AU - Pivetti, Christopher

AU - Lankford, Lee

AU - Chung, Karen

AU - Lee, Chelsey

AU - Chen, Y. Julia

AU - Kumar, Priyadarsini

AU - Vanover, Melissa

AU - Wang, Aijun

AU - Farmer, Diana L

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AB - Purpose: The purpose of this study was to investigate the effects of placental mesenchymal stromal cells (PMSCs) seeded on a clinical grade porcine small intestinal submucosa (SIS)-derived extracellular matrix (ECM) on hindlimb motor function in an ovine fetal repair model of myelomeningocele (MMC). Methods: MMC defects were surgically created in 21 fetuses at median gestational age 78 (range 76-83) days. Fetuses were randomly assigned to repair 25. days later with ECM only or PMSC-ECM. Surviving fetuses were delivered at term. Motor function was evaluated using the Sheep Locomotor Rating (SLR) scale (0-15). Histologic analysis of the spinal cord (SC) was completed. Results: Fetal viability was 71%. 5 of 8 (63%) lambs repaired with PMSC-ECM ambulated independently versus only 1 of 6 (17%) repaired with ECM only (p=0.04, χ2 test). SLR scores and large neuron densities were higher in the PMSC-ECM group. The cross-sectional areas of the SC and the gray matter were equally preserved. Conclusions: Fetal repair of MMC with PMSCs seeded on SIS-ECM improves hindlimb motor function in lambs. Using ECM helps to preserve the architecture of the SC, but adding PMSCs improves the lamb's ability to walk and increases large neuron density. Clinical studies are needed to show benefits in humans. Levels of evidence/type of study: Basic Science.

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