Dataset Information

Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele.

ABSTRACT:

Background/purpose

In 2004, a heritable occurrence of spina bifida was reported in sheep on a farm in the United States. We maintained and characterized the spina bifida phenotype in this flock to assess its potential as an alternative surgical model.

Methods

A breeding strategy was developed in which the sheep were crossed to maintain or increase the occurrence of spina bifida. Measurements and observations were recorded regarding lesion size, birthweight, ambulatory capacity, or urological function, and necropsies were performed on spina bifida afflicted lambs in conjunction with magnetic resonance imaging to determine the character of the spina bifida defects and assess the presence of Chiari-like malformations or hydrocephalus.

Results

The defects were observed to be more prevalent in ram lambs, and the rate of spina bifida per litter could be increased through backcrossing or by selection of a productive ewe breed. The lambs displayed a range of ambulatory and urological deficits which could be used to evaluate new fetal repair methodologies. Finally, affected lambs were shown to demonstrate severe Chiari malformations and hydrocephalus.

Conclusions

We have determined that use of these sheep as a natural source for spina bifida fetuses is feasible and could supplement the deficits of current sheep models for myelomeningocele repair.

Level of evidence

Level IV.

SUBMITTER: Steele JW

PROVIDER: S-EPMC6935438 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele.

Steele John W JW Bayliss Sharon S Bayliss John J Lin Ying Linda YL Wlodarczyk Bogdan J BJ Cabrera Robert M RM Asfaw Yohannes G YG Cummings Thomas J TJ Finnell Richard H RH George Timothy M TM

Journal of pediatric surgery 20190629 3

<h4>Background/purpose</h4>In 2004, a heritable occurrence of spina bifida was reported in sheep on a farm in the United States. We maintained and characterized the spina bifida phenotype in this flock to assess its potential as an alternative surgical model.<h4>Methods</h4>A breeding strategy was developed in which the sheep were crossed to maintain or increase the occurrence of spina bifida. Measurements and observations were recorded regarding lesion size, birthweight, ambulatory capacity, or ...[more]

PMID: 31301886

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Project description: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. 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. 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. The HUC as a skin patch for in utero spina bifida repair preserves spinal cord function by reducing underlying inflammation when compared to ADM.

Dataset Information

Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele.

Background/purpose

Methods

Results

Conclusions

Level of evidence

Publications

Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele.

Similar Datasets

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