Correction of hindbrain herniation and anatomy of the vermis after in utero repair of myelomeningocele in sheep

Bouchard, Sarah; Davey, Mary‐Ann; Rintoul, Natalie E.; Walsh, Danielle S.; Rorke, Lucy B.; Adzick, N. Scott

doi:10.1053/jpsu.2003.50078

Cited by 140 publications

(112 citation statements)

References 34 publications

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“…This finding suggests that future human fetal MMC treatment using cell sheet technology could potentially promote prenatal regeneration of the exposed neural tissues injured in utero and thus further improve the lifelong neurological outcomes currently achieved with fetal surgical repair 4 . Our conclusion is supported by the HE staining of tissue from the whole fetus in revealing that the adhering transplanted cell sheet remained viably attached to the fetal spinal cord at 4 hours after transplantation, with a well-preserved ECM.…”

Section: Discussionmentioning

confidence: 90%

A New Regenerative Approach to Fetal Myelomeningocele by Cell Sheet Transplantation

理絵

Irie

2017

Showa Univ J Med Sci

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: Myelomeningocele MMC is the most common form of congenital neural tube defect. Current fetal surgical repair performed to prevent the exposed spinal cord from being injured until delivery cannot reverse those injuries already in icted in utero.Cell sheet technology has been adopted successfully for the regeneration of diverse organs and tissues, although this promising modality has not yet been used for fetal therapy. This study thus tested our hypothesis that fetal MMC tissue histologically injured in utero could be regenerated using cell sheet technology. We used the L6 myoblast cell line derived from rat skeletal muscle for the cell sheet engineering. A fetal MMC model was also obtained from pregnant Sprague-Dawley SD rats fed orally with retinoic acid 60 mg / kg, embryonic day 10 . Cell sheets were then transplanted onto the fetal MMC lesion embryonic day 19 following maternal anesthesia, laparotomy, and hysterotomy. The incisional wound of the uterus was kept open for 4 hours under anesthesia with the MMC lesion maintained outside the body with the transplanted cell sheet. Subsequently, the experimental fetuses were sacri ced for histological HE stain and immunohistochemical studies to evaluate viability and differentiation potential based on cell markers of the transplanted L6 myoblasts. Immunohistochemical studies clearly demonstrated cell-sheet markers speci c to neurons, skeletal muscle, and myoblasts within the treated MMC lesions, confirming that the cell sheet was biologically implanted within 4 hours after the procedure. Cell sheet technology could be useful for intrauterine regeneration of the fetal rat spinal cord injured by an associated MMC.

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Section: Discussionmentioning

confidence: 90%

A New Regenerative Approach to Fetal Myelomeningocele by Cell Sheet Transplantation

理絵

Irie

2017

Showa Univ J Med Sci

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“…The simplified technique also allowed better preservation of the spinal cord cytoarchitecture. Several previous studies on the intrauterine correction of myelomeningocele had already suggested that prenatal correction led to a better preservation of the spinal cord and better clinical results (10)(11)(12)(13) .The MOMS study demonstrated that the intrauterine correction reduced the need of ventriculoperitoneal shunting from 82 to 40% comparing postnatal with prenatal correction, respectively. That study also showed better cognitive and motor skills up to 30 months of age in the group submitted to prenatal correction (6) .…”

Section: Discussionmentioning

confidence: 94%

Comparison between two surgical techniques for prenatal correction of meningomyelocele in sheep

Herrera

Leme

Valente

et al. 2012

Einstein (São Paulo)

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Objective: To compare the classical neurosurgical technique with a new simplified technique for prenatal repair of a myelomeningocelelike defect in sheep. Methods: A myelomeningocele-like defect (laminectomy and dural excision) was created in the lumbar region on day 90 of gestation in 9 pregnant sheep. Correction technique was randomized. In Group 1 the defect was corrected using the classic neurosurgical technique of three-layer suture (dura mater, muscle and skin closure) performed by a neurosurgeon. In Group 2, a fetal medicine specialist used a biosynthetic cellulose patch to protect the spinal cord and only the skin was sutured above it. Near term (day 132 of gestation) fetuses were sacrificed for pathological analysis. Results: There were two miscarriages and one maternal death. In total, six cases were available for pathological analysis, three in each group. In Group 1, there were adherence of the spinal cord to the scar (meningo-neural adhesion) and spinal cord architecture loss with posterior funiculus destruction and no visualization of grey matter. In Group 2, we observed in all cases formation of a neo-dura mater, separating the nervous tissue from adjacent muscles, and preserving the posterior funiculus and grey matter. Conclusion: The new simplified technique was better than the classic neurosurgical technique. It preserved the nervous tissue and prevented the adherence of the spinal cord to the scar. This suggests the current technique used for the correction of spina bifida in humans may need to be reassessed. de ovelhas. Métodos: Em 9 fetos, foi criado um defeito semelhante à mielomeningocele (laminectomia e excisão de dura-máter) no 90° dia de gestação. O tipo de correção foi randomizado. No Grupo 1, o defeito foi corrigido usando a técnica neurocirúrgica clássica, com a sutura de três camadas (dura-máter, músculo e pele), realizada por um neurocirurgião. No Grupo 2, um especialista em Medicina Fetal utilizou a técnica simplificada, colocando um fragmento de celulose biossintética sobre a medula e suturando apenas da pele sobre a celulose. Próximo ao termo da gestação (132 dias), os fetos foram sacrificados para análise anatomopatológica. Resultados: Ocorreram dois casos de aborto e uma morte materna, restando seis casos para avaliação -três em cada grupo. No Grupo 1, todos os casos mostraram aderência da medula à cicatriz (meningoadesão) e perda da arquitetura medular, com destruição do funículo posterior e perda da visualização da substância cinzenta. No Grupo 2, observou-se, em todos os casos, a formação de uma neodura-máter, separando o tecido nervoso do músculo adjacente, sendo que o funículo posterior e a substância cinzenta estavam preservados. Conclusão: A técnica simplificada foi superior à neurocirúrgica, com maior preservação da medula e evitando as aderências do tecido nervoso. Os presentes achados sugerem que a técnica utilizada atualmente na correção de mielomeningocele em fetos humanos deva ser reavaliada. Keywords

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“…This often needs to be replaced as the child grows because of problems with blockage and infection. [53][54][55][56][57] The prognosis for babies born with OSB depends on the location, size and extent of the defect and the presence of hydrocephalus, and the range of disability caused is variable. Still, it often leads to severe disability.…”

mentioning

confidence: 99%

“…Generally, abnormalities higher on the spine produce a greater risk of paralysis and other debilitating complications. [53][54][55][56][57] Nowadays, all women are advised to take a supplement of 400 mg of folic acid for at least 3 months before preg nancy and up to the end of the 12th week of pregnancy. 58 Women who have a family history of NTDs are advised to take a higher dose of 5 mg of folic acid, as this has been shown to reduce their chances or having another baby with an NTD.…”

mentioning

confidence: 99%

First Trimester Anomaly Scan—The Last Redoubt Won: Open Spina Bifida

Novac¹,

Tudorache²,

Gabriel³

et al. 2015

Donald School Journal of Ultrasound in Obstetrics and Gynecology

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Open spina bifida (OSB) is a non-lethal fetal anomaly, yet often leads to severe disability. Most cases of open spina bifida are detected at the second trimester fetal anomaly ultrasound scan. The 11 to 13 weeks of amenorrhea scan evolved over the last 20 years from essentially a dating scan, to a genetic scan, and recently to one which includes, in addition to the genetic markers, a basic checklist for examination of the whole fetal anatomy. The direct visualization of the spine at the first trimester (FT) scan remained difficult, despite the wider use of high-reso lution ultrasound machines and the volumetric approach. Thus, indirect intracranial morphological markers for OSB were proposed to diagnose this neural tube defect.The present review aims to describe the specific anatomical feature of the spine and the posterior brain, both on parasagittal and on axial planes, recently proposed for the early detection of OSB.Specialists involved in the prenatal diagnosis will eventually elaborate in the future a screening protocol for OSB in the FT of pregnancy, using the most valuable and easy to obtain marker, in a single 2D plane.The offer of an early diagnosis of possible severe anomalies, such as OSB, is a tool enhancing the autonomy of the pregnant woman.

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Correction of hindbrain herniation and anatomy of the vermis after in utero repair of myelomeningocele in sheep

Cited by 140 publications

References 34 publications

A New Regenerative Approach to Fetal Myelomeningocele by Cell Sheet Transplantation

A New Regenerative Approach to Fetal Myelomeningocele by Cell Sheet Transplantation

Comparison between two surgical techniques for prenatal correction of meningomyelocele in sheep

First Trimester Anomaly Scan—The Last Redoubt Won: Open Spina Bifida

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