PMID- 36964735 OWN - NLM STAT- MEDLINE DCOM- 20231025 LR - 20231027 IS - 1933-0693 (Electronic) IS - 0022-3085 (Linking) VI - 139 IP - 4 DP - 2023 Oct 1 TI - Cryopreserved human umbilical cord as a meningeal patch during in utero spina bifida repair in a modified ovine model. PG - 1169-1179 LID - 10.3171/2023.2.JNS222928 [doi] AB - OBJECTIVE: Despite in utero spina bifida (SB) repair, more than two-thirds of patients with SB are unable to ambulate independently, and 1 in 4 children need surgery for tethered cord by school age. The objective of this study was to test the cryopreserved human umbilical cord (HUC) as an antiscarring material to reduce tethering and improve function in a modified in utero SB repair model. METHODS: An SB defect (L2-6 levels) without myelotomy was created in fetuses of timed-pregnant ewes at gestational day (GD) 75. On GD 96, the fetal defect was exposed, and the arachnoid layer was removed to disrupt the barrier and expose the spinal cord to simulate human in utero SB repair. The fetuses were randomly assigned to two groups according to the method used to cover the spinal cord: the conventional repair (CR) group, for which myofascial closure was used (n = 7), and the HUC meningeal patch group, for which HUC was used as a meningeal patch (n = 6), followed by primary skin closure. The lambs were delivered at GD 140. Blinded clinical assessment of spinal cord function was performed using the Texas Spinal Cord Injury Scale (TSCIS). Histology of the spine was performed for quantitative assessment of spinal cord tethering, inflammatory markers, and arachnoid layer regeneration. RESULTS: The TSCIS scores were significantly lower in the CR than the HUC meningeal patch group (p = 0.0015) and the controls (p = 0.0018). The loss of spinal cord function in the CR group was mainly due to ataxia and loss of proprioception (p = 0.01 and 0.005 vs control and HUC, respectively). The histology at the repair site showed higher rates of spinal cord tethering in the CR lambs than the HUC lambs at all levels of the repair site (p = 0.01 and 0.02 vs control and HUC, respectively). In the CR with tethering compared with the HUC repair, there was a lower arachnoid layer covering at the repair site (p = 0.001). There was greater astrocyte activation in the posterior column in the CR than in the HUC repair group (p = 0.01). CONCLUSIONS: In a modified ovine SB model, the HUC as a meningeal patch allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero SB repair. FAU - Mann, Lovepreet K AU - Mann LK AD - 1Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Fetal Intervention, UTHealth Houston, The University of Texas McGovern Medical School, Houston. AD - 2The Fetal Center at Children's Memorial Hermann Hospital, Houston. FAU - Won, Jong H AU - Won JH AD - 1Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Fetal Intervention, UTHealth Houston, The University of Texas McGovern Medical School, Houston. AD - 2The Fetal Center at Children's Memorial Hermann Hospital, Houston. FAU - Garnett, Jeannine AU - Garnett J AD - 1Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Fetal Intervention, UTHealth Houston, The University of Texas McGovern Medical School, Houston. AD - 2The Fetal Center at Children's Memorial Hermann Hospital, Houston. FAU - Patel, Rajan P AU - Patel RP AD - Departments of3Diagnostic and Interventional Imaging and. FAU - Narayana, Ponnada A AU - Narayana PA AD - Departments of3Diagnostic and Interventional Imaging and. FAU - Jain, Ranu AU - Jain R AD - 2The Fetal Center at Children's Memorial Hermann Hospital, Houston. AD - 4Anesthesia, UTHealth Houston, The University of Texas McGovern Medical School, Houston; and. FAU - Fletcher, Stephen A AU - Fletcher SA AD - 2The Fetal Center at Children's Memorial Hermann Hospital, Houston. AD - 5Department of Pediatric Surgery, Division of Pediatric Neurosurgery, UTHealth Houston, The University of Texas McGovern Medical School, Houston, Texas. FAU - Papanna, Ramesha AU - Papanna R AD - 1Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Fetal Intervention, UTHealth Houston, The University of Texas McGovern Medical School, Houston. AD - 2The Fetal Center at Children's Memorial Hermann Hospital, Houston. LA - eng GR - R21 HD092754/HD/NICHD NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20230324 PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 SB - IM MH - Animals MH - Child MH - Female MH - Humans MH - Pregnancy MH - Cryopreservation MH - Neurosurgical Procedures/methods MH - Sheep MH - Spinal Cord/surgery MH - *Spinal Dysraphism/surgery/pathology MH - Umbilical Cord/pathology OTO - NOTNLM OT - antiscarring OT - arachnoid layer regeneration OT - cryopreserved human umbilical cord patch OT - in utero repair OT - spina bifida OT - spinal cord tethering OT - surgical technique EDAT- 2023/03/26 06:00 MHDA- 2023/10/23 12:43 CRDT- 2023/03/25 07:22 PHST- 2022/12/30 00:00 [received] PHST- 2023/02/06 00:00 [accepted] PHST- 2023/10/23 12:43 [medline] PHST- 2023/03/26 06:00 [pubmed] PHST- 2023/03/25 07:22 [entrez] AID - 10.3171/2023.2.JNS222928 [doi] PST - epublish SO - J Neurosurg. 2023 Mar 24;139(4):1169-1179. doi: 10.3171/2023.2.JNS222928. Print 2023 Oct 1.