PMID- 34768448 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211118 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 10 IP - 21 DP - 2021 Oct 25 TI - Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model. LID - 10.3390/jcm10214928 [doi] LID - 4928 AB - OBJECTIVES: Use of off-label tissue graft materials, such as acellular dermal matrix (ADM), for in utero repair of severe spina bifida (SB), where primary skin layer closure is not possible, is associated with poor neurological outcomes. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties, and provides watertight SB repair. We tested the hypothesis that the HUC is a superior skin patch to ADM for reducing inflammation at the repair site and preserving spinal cord function. METHODS: In timed-pregnant ewes with twins, on gestational day (GD) 75, spina bifida was created without a myelotomy (functional model). On GD 95, repair was performed using HUC vs. ADM patches (randomly assigned) by suturing them to the skin edges. Additionally, full thickness skin closure as a primary skin closure (PSC) served as a positive control. Delivery was performed on GD 140, followed by blinded to treatment neurological assessments of the lambs using the Texas Spinal Cord Injury Scale (TSCIS) for gait, proprioception, and nociception. Lambs without spina bifida were used as controls (CTL). Ex vivo magnetic resonance imaging of spines at the repair site were performed, followed by quantitative pathological assessments. Histological assessments (blinded) included Masson's trichrome, and immunofluorescence for myeloperoxidase (MPO; neutrophils) and for reactive astrocytes (inflammation) by co-staining vimentin and GFAP. RESULTS: The combined hind limbs' TSCIS was significantly higher in the HUC group than in ADM and PSC groups, p = 0.007. Both ADM and PSC groups exhibited loss of proprioception and mild to moderate ataxia compared to controls. MRI showed increased pathological findings in the PSC group when compared to the HUC group, p = 0.045. Histologically, the meningeal layer was thickened (inflammation) by 2-3 fold in ADM and PSC groups when compared to HUC and CTL groups, p = 0.01. There was lower MPO positive cells in the HUC group than in the ADM group, p = 0.018. Posterior column astrocyte activation was increased in ADM and PSC lambs compared to HUC lambs, p = 0.03. CONCLUSION: The HUC as a skin patch for in utero spina bifida repair preserves spinal cord function by reducing underlying inflammation when compared to ADM. FAU - Mann, Lovepreet K AU - Mann LK AD - Division of Maternal-Fetal Medicine, The Fetal Center at Children's Memorial Hermann Hospital, Department of Obstetrics, Gynecology and Reproductive Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Won, Jong Hak AU - Won JH AD - Division of Maternal-Fetal Medicine, The Fetal Center at Children's Memorial Hermann Hospital, Department of Obstetrics, Gynecology and Reproductive Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Patel, Rajan AU - Patel R AUID- ORCID: 0000-0002-0891-1541 AD - Department of Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Bergh, Eric P AU - Bergh EP AUID- ORCID: 0000-0001-6276-854X AD - Division of Maternal-Fetal Medicine, The Fetal Center at Children's Memorial Hermann Hospital, Department of Obstetrics, Gynecology and Reproductive Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Garnett, Jeannine AU - Garnett J AD - Division of Maternal-Fetal Medicine, The Fetal Center at Children's Memorial Hermann Hospital, Department of Obstetrics, Gynecology and Reproductive Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Bhattacharjee, Meenakshi B AU - Bhattacharjee MB AD - Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Narayana, Ponnada A AU - Narayana PA AUID- ORCID: 0000-0002-5703-4346 AD - Department of Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Jain, Ranu AU - Jain R AD - Department of Anesthesia, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Fletcher, Stephen A AU - Fletcher SA AD - Division of Pediatric Neurosurgery, Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Lai, Dejian AU - Lai D AD - Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. FAU - Papanna, Ramesha AU - Papanna R AUID- ORCID: 0000-0002-3801-346X AD - Division of Maternal-Fetal Medicine, The Fetal Center at Children's Memorial Hermann Hospital, Department of Obstetrics, Gynecology and Reproductive Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. LA - eng GR - R21AR073509/NH/NIH HHS/United States GR - 1R01HD105173/NH/NIH HHS/United States GR - xxx/Departmental funds from the Obstetrics, Gynecology and Reproductive Sciences at UTHealth, McGovern Medical School at Houston/ PT - Journal Article DEP - 20211025 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC8584988 OTO - NOTNLM OT - acellular dermal matrix OT - astrocyte activation OT - conventional repair OT - inflammation OT - regenerative healing OT - sheep spina bifida repair model OT - umbilical cord COIS- The authors declare no conflict of interest. EDAT- 2021/11/14 06:00 MHDA- 2021/11/14 06:01 PMCR- 2021/10/25 CRDT- 2021/11/13 01:01 PHST- 2021/09/16 00:00 [received] PHST- 2021/10/17 00:00 [revised] PHST- 2021/10/19 00:00 [accepted] PHST- 2021/11/13 01:01 [entrez] PHST- 2021/11/14 06:00 [pubmed] PHST- 2021/11/14 06:01 [medline] PHST- 2021/10/25 00:00 [pmc-release] AID - jcm10214928 [pii] AID - jcm-10-04928 [pii] AID - 10.3390/jcm10214928 [doi] PST - epublish SO - J Clin Med. 2021 Oct 25;10(21):4928. doi: 10.3390/jcm10214928.