Lucie Guilbaud1, Anaïs Dugas2, Mathilde Weber3, Carole Deflers3, Pauline Lallemant4, Thomas Lilin5, Clovis Adam6, Audrey Cras7, Miryam Mebarki3, Michel Zérah8, Lionel Faivre3, Jérôme Larghero3, Jean-Marie Jouannic9. 1. Paris University, AP-HP, Hôpital Saint-Louis, Unité de Thérapie Cellulaire et Centre MEARY de Thérapie Cellulaire et Génique, Paris, France; Stem Cell Biotechnologies, U976 et Centre d'Investigation Clinique en Biothérapies CIC-BT CBT501, INSERM, Paris, France; Sorbonne University, AP-HP, Trousseau Hospital, DMU ORIGYNE, Department of Fetal Medicine, Paris, France; National Reference Center for Rare Disease: Vertebral and Spinal Cord Anomalies (MAVEM Center), AP-HP, Trousseau Hospital, Paris, France. Electronic address: lucie.guilbaud@aphp.fr. 2. Paris University, AP-HP, Hôpital Saint-Louis, Unité de Thérapie Cellulaire et Centre MEARY de Thérapie Cellulaire et Génique, Paris, France; Stem Cell Biotechnologies, U976 et Centre d'Investigation Clinique en Biothérapies CIC-BT CBT501, INSERM, Paris, France; Sorbonne University, AP-HP, Trousseau Hospital, DMU ORIGYNE, Department of Fetal Medicine, Paris, France; National Reference Center for Rare Disease: Vertebral and Spinal Cord Anomalies (MAVEM Center), AP-HP, Trousseau Hospital, Paris, France. 3. Paris University, AP-HP, Hôpital Saint-Louis, Unité de Thérapie Cellulaire et Centre MEARY de Thérapie Cellulaire et Génique, Paris, France; Stem Cell Biotechnologies, U976 et Centre d'Investigation Clinique en Biothérapies CIC-BT CBT501, INSERM, Paris, France. 4. National Reference Center for Rare Disease: Vertebral and Spinal Cord Anomalies (MAVEM Center), AP-HP, Trousseau Hospital, Paris, France; Sorbonne University, AP-HP, Trousseau Hospital, Department of Physical Medicine and Rehabilitation, Paris, France. 5. Center for Biomedical Research, National Veterinary School, Maisons Alfort, France. 6. Paris Saclay University, Kremlin Bicêtre Hospital, Department of Pathology, Le Kremlin-Bicêtre, France. 7. Paris University, AP-HP, Hôpital Saint-Louis, Unité de Thérapie Cellulaire et Centre MEARY de Thérapie Cellulaire et Génique, Paris, France; Paris university, Innovative Therapies in Haemostasis, UMR1140 and Centre d'Investigation Clinique en Biothérapies CIC-BT CBT501, INSERM, Paris, France. 8. National Reference Center for Rare Disease: Vertebral and Spinal Cord Anomalies (MAVEM Center), AP-HP, Trousseau Hospital, Paris, France; Paris University, AP-HP, Necker Enfants Malades Hospital, Department of Pediatric Neurosurgery, 149 Rue de Sèvres, 75015 Paris, France. 9. Sorbonne University, AP-HP, Trousseau Hospital, DMU ORIGYNE, Department of Fetal Medicine, Paris, France; National Reference Center for Rare Disease: Vertebral and Spinal Cord Anomalies (MAVEM Center), AP-HP, Trousseau Hospital, Paris, France.
Abstract
PURPOSE OF THE STUDY: The purpose of our study was to investigate the effects of ovine umbilical cord-derived mesenchymal stromal cells (UC-MSCs) seeded in a fibrin patch as an adjuvant therapy for fetal myelomeningocele repair in the ovine model. MATERIALS AND METHODS: MMC defects were surgically created at 75 days of gestation and repaired 15 days later with UC-MSCs patch or an acellular patch. At birth, motor function, tail movements, and voiding abilities were recorded. Histological and immunohistochemical analysis included study of MMC defect's healing, spinal cord, UC-MSCs survival, and screening for tumors. RESULTS: Six lambs were born alive in each group. There was no difference between the two groups on the median sheep locomotor rating score but all lambs in the control group had a score between lower than 3 compared to 50% in UC-MSCs group. There were more lambs with tail movements and voiding ability in UC-MSCs group (83% vs 0% and 50% vs 0%, respectively). gray matter area and large neurons density were higher in UC-MSCs group (2.5 vs 0.8 mm2 and 19.3 vs 1.6 neurons/mm2 of gray matter, respectively). Fibrosis thickness at the myelomeningocele scar level was reduced in UC-MSCs group (1269 µm vs 2624 µm). No tumors were observed. CONCLUSION: Fetal repair of myelomeningocele using allogenic UC-MSCs patch provides a moderate improvement in neurological functions, gray matter and neuronal preservation and prevented from fibrosis development at the myelomeningocele scar level.
PURPOSE OF THE STUDY: The purpose of our study was to investigate the effects of ovine umbilical cord-derived mesenchymal stromal cells (UC-MSCs) seeded in a fibrin patch as an adjuvant therapy for fetal myelomeningocele repair in the ovine model. MATERIALS AND METHODS: MMC defects were surgically created at 75 days of gestation and repaired 15 days later with UC-MSCs patch or an acellular patch. At birth, motor function, tail movements, and voiding abilities were recorded. Histological and immunohistochemical analysis included study of MMC defect's healing, spinal cord, UC-MSCs survival, and screening for tumors. RESULTS: Six lambs were born alive in each group. There was no difference between the two groups on the median sheep locomotor rating score but all lambs in the control group had a score between lower than 3 compared to 50% in UC-MSCs group. There were more lambs with tail movements and voiding ability in UC-MSCs group (83% vs 0% and 50% vs 0%, respectively). gray matter area and large neurons density were higher in UC-MSCs group (2.5 vs 0.8 mm2 and 19.3 vs 1.6 neurons/mm2 of gray matter, respectively). Fibrosis thickness at the myelomeningocele scar level was reduced in UC-MSCs group (1269 µm vs 2624 µm). No tumors were observed. CONCLUSION: Fetal repair of myelomeningocele using allogenic UC-MSCs patch provides a moderate improvement in neurological functions, gray matter and neuronal preservation and prevented from fibrosis development at the myelomeningocele scar level.