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

2021 ◽  
Vol 10 (21) ◽  
pp. 4928
Author(s):  
Lovepreet K. Mann ◽  
Jong Hak Won ◽  
Rajan Patel ◽  
Eric P. Bergh ◽  
Jeannine Garnett ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spina Bifida ◽  
Functional Model ◽  
In Utero ◽  
Human Umbilical Cord ◽  
Skin Closure ◽  
Repair Site ◽  
Skin Patch ◽  
Cord Injury ◽  
Spinal Cord Function

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.

Cryopreserved human umbilical cord versus acellular dermal matrix patches for in utero fetal spina bifida repair in a pregnant rat model

2020 ◽  
Vol 32 (2) ◽  
pp. 321-331
Author(s):  
Lovepreet K. Mann ◽  
Jong H. Won ◽  
Nicholaus J. Trenton ◽  
Jeannine Garnett ◽  
Saul Snowise ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Acellular Dermal Matrix ◽  
In Utero ◽  
Patch Repair ◽  
Human Umbilical Cord ◽  
Dermal Matrix ◽  
Meningeal Cells ◽  
Spinal Cord Function ◽  
Repair Group

OBJECTIVEDespite significant improvement in spinal cord function after in utero spina bifida (SB) repair compared with traditional postnatal repair, over half of the children who undergo this procedure do not benefit completely. This lack of benefit has been attributed to closure methods of the defect, with subsequent spinal cord tethering at the repair site. Hence, a regenerative patch or material with antiinflammatory and anti-scarring properties may alleviate comorbidities with improved outcomes. The authors’ primary objective was therefore to compare cryopreserved human umbilical cord (HUC) versus acellular dermal matrix (ADM) patches for regenerative repair of in utero SB lesions in an animal model.METHODSIn vivo studies were conducted in retinoic acid–induced SB defects in fetuses of Sprague-Dawley rats. HUC or ADM patches were sutured over the SB defects at a gestational age of 20 days. Repaired SB defect tissues were harvested after 48–52 hours. Tissue sections were immunofluorescently stained for the presence of neutrophils, macrophages, keratinocytes, meningeal cells, and astrocytes and for any associated apoptosis. In vitro meningeal or keratinocyte cell coculture experiments with the ADM and HUC patches were performed. All experiments were scored quantitatively in a blinded manner.RESULTSNeutrophil counts and apoptotic cells were lower in the HUC-based repair group (n = 8) than in the ADM patch repair group (n = 7). In the HUC patch repair group, keratinocytes were present on the outer surface of the patch, meningeal cells were present on the inner surface of the patch adjacent to the neural placode, and astrocytes were noted to be absent. In the ADM patch repair group, all 3 cell types were present on both surfaces of the patch. In vitro studies showed that human meningeal cells grew preferentially on the mesenchymal side of the HUC patch, whereas keratinocytes showed tropism for the epithelial side, suggesting an inherent HUC-based cell polarity. In contrast, the ADM patch studies showed no polarity and decreased cellular infiltration.CONCLUSIONSThe HUC patch demonstrated reduced acute inflammation and apoptosis together with superior organization in regenerative cellular growth when compared with the ADM patch, and is therefore likely the better patch material for in utero SB defect repair. These properties may make the HUC biomaterial useful as a “meningeal patch” during spinal cord surgeries, thereby potentially reducing tethering and improving on spinal cord function.

scholarly journals Intraspinal Injection of Platelet-Rich Plasma Promotes Regeneration of the Spinal Cord and Improves Locomotor Function by Modulating the Apoptosis and the Wnt Signaling Pathways

2021 ◽  
Author(s):  
Zahra Behroozi ◽  
Fatemeh Ramezani ◽  
farinaz Nasirinezhad
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Wnt Signaling ◽  
Motor Function ◽  
Platelet Rich Plasma ◽  
Wnt Signaling Pathway ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Locomotor Function ◽  
Cord Injury

Abstract Background: There are complex mechanisms for reducing intrinsic repair ability and neuronal regeneration following spinal cord injury (SCI). Platelet-rich plasma (PRP) is a rich source of growth factors and has been used to stimulate regeneration of peripheral nerves in degenerationtive diseases. However, only a few studies have investigated the effects of PRP on the SCI models. We examined whether PRP derived from human umbilical cord blood (HUCB-PRP) could recover motor function in animals with spinal cord injury. We also investigate the role of Wnt signaling pathway.Methods: Ault male Wistar rats were randomly divided into 6 groups (n=60) as control, sham, SCI, vehicle (SCI+platelet-poor plasma), PRP2day (SCI+injection 2 days after SCI) and PRP14day (SCI+injection 14 days after SCI). SCI was performed at the T12-T13 level. BBB tests were done weekly after injury for six weeks. caspase3 expression was determined using the Immunohistochemistry technique. The expression of GSK3β, Tau and MAG were determined using the Western blot technique. Data were analyzed by PRISM & SPSS software. Results: PRP injected animals showed a higher locomotor function recovery than those in the SCI group (p<0.0001). The level of caspase3, GSK3β and CSF- Tau reduced and MAG level in the spinal cord increased by injection of HUCB-PRP in animals with spinal cord injury. Conclusions: Injection of HUCB-PRP enhanced hind limb locomotor performance by modulation of caspase3, GSK3β, tau and MAG expression. Using HUCB-PRP could be a new therapeutic option for recovering the motor function and axonal regeneration after spinal cord injury.

scholarly journals Neurological Outcomes after Human Umbilical Cord Patch for In Utero Spina Bifida Repair in a Sheep Model

2016 ◽  
Vol 06 (03) ◽  
pp. e309-e317 ◽  
Author(s):  
Lovepreet Mann ◽  
Saul Snowise ◽  
Yisel Morales ◽  
Sanjay Prabhu ◽  
Scheffer Tseng ◽  
...  
Keyword(s):  
Spina Bifida ◽  
Umbilical Cord ◽  
In Utero ◽  
Human Umbilical Cord ◽  
Sheep Model ◽  
Neurological Outcomes

Managing spinal cord trauma

2019 ◽  
pp. 781-788
Author(s):  
Saksith Smithason ◽  
Bryan S. Lee ◽  
Edward C. Benzel
Keyword(s):  
Spinal Cord ◽  
Cell Damage ◽  
Spinal Cord Trauma ◽  
Prolonged Hospital Stay ◽  
Cord Injury ◽  
Prolonged Hospital ◽  
Adequate Management ◽  
Spinal Cord Function ◽  
Underlying Pathophysiology

Spinal cord injury (SCI), either traumatic or non-traumatic in aetiology, leads to temporary or permanent damage to the spinal cord function. Significant efforts have been directed towards the elucidation of the underlying pathophysiology of SCI. Both primary and secondary mechanisms of SCI exist, leading to immediate and often irreversible cell damage. Immediate treatment and adequate management in the setting of acute SCI are essential, preservation of even a small amount of functional neuronal tissue can permit ambulation. SCI is associated with a prolonged hospital stay, rehabilitation stay, and often associated with enormous monetary costs. Neurological recovery after SCI is largely dependent on the extent of injury. The management of SCI and the determination of the role and timing of surgical decompression remain crucial and yet controversial. Further epidemiological research and studies are warranted in order to enhance healthcare planning and cost-effectiveness.

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