Long-term safety evaluation of placental mesenchymal stromal cells for in utero repair of myelomeningocele in a novel ovine model

Sarah C. Stokes, Christina M. Theodorou, Jordan E. Jackson, Christopher Pivetti, Priyadarsini Kumar, Kaeli J. Yamashiro, Zachary J. Paxton, Lizette Reynaga, Alicia Hyllen, Aijun Wang, Diana L. Farmer

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Augmentation of in utero myelomeningocele repair with human placental mesenchymal stromal cells seeded onto extracellular matrix (PMSC-ECM) improves motor outcomes in an ovine myelomeningocele model. This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial. Methods: Laminectomy of L5-L6 with PMSC-ECM placement directly onto the spinal cord was performed in five fetal lambs at gestational age (GA) 100–106 days. Lambs and ewes were monitored for three months following delivery. Lambs underwent magnetic resonance imaging (MRI) of the brain and spine at birth and at three months. All organs from lambs and uteri from ewes underwent histologic evaluation. Lamb spinal cords and brains and ewe placentas were evaluated for persistence of PMSCs by polymerase chain reaction for presence of human DNA. Results: MRIs demonstrated no evidence of abnormal tissue growth or spinal cord tethering. Histological analysis demonstrated no evidence of abnormal tissue growth or treatment related adverse effects. No human DNA was identified in evaluated tissues. Conclusion: There was no evidence of abnormal tissue growth or PMSC persistence at three months following in utero application of PMSC-ECM to the spinal cord. This supports proceeding with clinical trials of PMSC-ECM for in utero myelomeningocele repair. Level of evidence: N/A Type of study: Basic science

Original languageEnglish (US)
JournalJournal of pediatric surgery
DOIs
StateAccepted/In press - 2021

Keywords

  • Fetal surgery
  • Mesenchymal stomal cell
  • Myelomeningocele
  • Safety
  • Spina bifida

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

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