In utero treatment of myelomeningocele with allogenic umbilical cord-derived mesenchymal stromal cells in an ovine model

Lucie Guilbaud; Anaïs Dugas; Mathilde Weber; Carole Deflers; Pauline Lallemant; Thomas Lilin; Clovis Adam; Audrey Cras; Miryam Mebarki; Michel Zérah; Lionel Faivre; Jérôme Larghero; Jean-Marie Jouannic

doi:10.1016/j.retram.2021.103314

In utero treatment of myelomeningocele with allogenic umbilical cord-derived mesenchymal stromal cells in an ovine model

Curr Res Transl Med. 2022 Jan;70(1):103314. doi: 10.1016/j.retram.2021.103314. Epub 2021 Oct 31.

Authors

Affiliations

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: [email protected].
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.

PMID: 34731725
DOI: 10.1016/j.retram.2021.103314

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.

Keywords: Fetal stem cell; Fetal surgery; Mesenchymal stromal cells; Myelomeningocele; Ovine model; Spina bifida; Umbilical cord.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Fetus
Meningomyelocele* / therapy
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells*
Sheep
Umbilical Cord