Sarah C Stokes1, Christina M Theodorou2, Jordan E Jackson2, Christopher Pivetti3, Priyadarsini Kumar3, Kaeli J Yamashiro2, Zachary J Paxton3, Lizette Reynaga3, Alicia Hyllen3, Aijun Wang4, Diana L Farmer5. 1. Division of Pediatric General, Thoracic and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, 2335 Stockton Blvd, Room 5107, Sacramento, CA 95817, USA. Electronic address: scstokes@ucdavis.edu. 2. Division of Pediatric General, Thoracic and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, 2335 Stockton Blvd, Room 5107, Sacramento, CA 95817, USA. 3. Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA. 4. Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA; Shriners Hospital for Children Northern California, 3425 Stockton Blvd, Sacramento, CA 95817, USA. 5. Division of Pediatric General, Thoracic and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, 2335 Stockton Blvd, Room 5107, Sacramento, CA 95817, USA; Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA; Shriners Hospital for Children Northern California, 3425 Stockton Blvd, Sacramento, CA 95817, USA.
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.
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.
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