Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model

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 regener...

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Autores principales:	Lovepreet K. Mann, Jong Hak Won, Rajan Patel, Eric P. Bergh, Jeannine Garnett, Meenakshi B. Bhattacharjee, Ponnada A. Narayana, Ranu Jain, Stephen A. Fletcher, Dejian Lai, Ramesha Papanna
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	umbilical cord regenerative healing sheep spina bifida repair model inflammation astrocyte activation acellular dermal matrix Medicine R
Acceso en línea:	https://doaj.org/article/cee9d62f98f54422a804eedc7e48d1b9
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spelling	oai:doaj.org-article:cee9d62f98f54422a804eedc7e48d1b92021-11-11T17:33:59ZAllografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model10.3390/jcm102149282077-0383https://doaj.org/article/cee9d62f98f54422a804eedc7e48d1b92021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/4928https://doaj.org/toc/2077-0383Objectives: 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, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.01. There was lower MPO positive cells in the HUC group than in the ADM group, <i>p</i> = 0.018. Posterior column astrocyte activation was increased in ADM and PSC lambs compared to HUC lambs, <i>p</i> = 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.Lovepreet K. MannJong Hak WonRajan PatelEric P. BerghJeannine GarnettMeenakshi B. BhattacharjeePonnada A. NarayanaRanu JainStephen A. FletcherDejian LaiRamesha PapannaMDPI AGarticleumbilical cordregenerative healingsheep spina bifida repair modelinflammationastrocyte activationacellular dermal matrixMedicineRENJournal of Clinical Medicine, Vol 10, Iss 4928, p 4928 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	umbilical cord regenerative healing sheep spina bifida repair model inflammation astrocyte activation acellular dermal matrix Medicine R
spellingShingle	umbilical cord regenerative healing sheep spina bifida repair model inflammation astrocyte activation acellular dermal matrix Medicine R Lovepreet K. Mann Jong Hak Won Rajan Patel Eric P. Bergh Jeannine Garnett Meenakshi B. Bhattacharjee Ponnada A. Narayana Ranu Jain Stephen A. Fletcher Dejian Lai Ramesha Papanna Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
description	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, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.01. There was lower MPO positive cells in the HUC group than in the ADM group, <i>p</i> = 0.018. Posterior column astrocyte activation was increased in ADM and PSC lambs compared to HUC lambs, <i>p</i> = 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.
format	article
author	Lovepreet K. Mann Jong Hak Won Rajan Patel Eric P. Bergh Jeannine Garnett Meenakshi B. Bhattacharjee Ponnada A. Narayana Ranu Jain Stephen A. Fletcher Dejian Lai Ramesha Papanna
author_facet	Lovepreet K. Mann Jong Hak Won Rajan Patel Eric P. Bergh Jeannine Garnett Meenakshi B. Bhattacharjee Ponnada A. Narayana Ranu Jain Stephen A. Fletcher Dejian Lai Ramesha Papanna
author_sort	Lovepreet K. Mann
title	Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
title_short	Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
title_full	Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
title_fullStr	Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
title_full_unstemmed	Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model
title_sort	allografts for skin closure during in utero spina bifida repair in a sheep model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cee9d62f98f54422a804eedc7e48d1b9
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Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model

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