Morphology of nervous lesion in the spinal cord and bladder of fetal rats with myelomeningocele at different gestational age

Shen, Jian; Zhou, Guomin; Chen, Hong; Bi, Yunli

doi:10.1016/j.jpedsurg.2013.08.021

Cited by 14 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, low expression levels of β-III-tubulin and α-SMA protein were detected subsequent to prenatal MMC repair using a rat model, which suggested damage to the smooth muscle and nerves of the bladder in the MMC fetal rats. This observation was in accordance with the results of Danzer et al ( 14 , 30 ) and Shen et al ( 15 ). In addition, high expression of AChE in the MMC fetal rats indicated developmental abnormalities of the cholinergic nerve or neuromuscular junction; however, in utero repair did not induce a significant decrease in AChE mRNA expression.…”

Section: Discussionsupporting

confidence: 94%

“…The control and MMC groups had 8 rats each, while 115 rats were prepared for the MMC repair group. The MMC fetal rat model was established by intragastric administration pregnant rats with all-trans retinoic acid (ATRA; Sigma Aldrich; Merck, Shanghai, China) dissolved in 2.0 ml olive oil at a dose of 60 mg/kg body weight at stage E9.5 ( 13 – 15 ). Control rats were treated with 2.0 ml olive oil by intragastric administration at E9.5.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

In utero repair of fetal rat myelomeningocele affects neuromuscular development in the bladder

Tang

Zhong

Chen

et al. 2017

Experimental and Therapeutic Medicine

Self Cite

View full text Add to dashboard Cite

Fetal repair of myelomeningocele (MMC) has been proven to be beneficial for the central nervous system development; however, the effect of fetal MMC repair on bladder function remains controversial. The objective of the present study was to establish an early timepoint for in utero MMC repair using a rat model, and to investigate the changes in bladder development subsequent to that intervention. Sprague Dawley rats were divided into the MMC, MMC repair and control groups. MMC rat fetus models were created by treating pregnant rats with all-trans retinoic acid. The MMC defect was then repaired in utero at embryonic day 17 (E17) using a chitosan-gelatin membrane patch. Fetal rat bladders were removed at E19 and E21 in each group, as well as at stage E17 in the MMC and control groups. Differential expression of β-III-tubulin, α-smooth muscle actin (α-SMA), nerve growth factor (NGF) and acetylcholinesterase (AChE) mRNA, and β-III-tubulin and α-SMA protein in the bladder following fetal repair was measured and compared among the three groups. In addition, the expression of NGF mRNA was significantly elevated at E21 in the MMC group compared with that of the control group, however, the level decreased in the repair group at stage E21. The expression of α-SMA mRNA significantly increased at E19 and then decreased at E21 in the repair group compared with that of the MMC group; however, there were no significant changes in α-SMA protein following the repair. Furthermore, the repair enhanced β-III-tubulin mRNA expression at E19, but ameliorated the decrease of β-III-tubulin protein at E21. The expression of AChE mRNA increased in the MMC group at E19 and E21 compared with that of the control group, although it was not significantly altered following repair as compared with that of the MMC group. In conclusion, in the current study, abnormal neuromuscular development was observed in the MMC bladder, which enabled a certain degree of improvement in the in utero MMC repair.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

In utero repair of fetal rat myelomeningocele affects neuromuscular development in the bladder

Tang

Zhong

Chen

et al. 2017

Experimental and Therapeutic Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…This ''experiment of nature'' confirms that spinal cord function is present in early gestation and is progressively diminished during later stages of gestation until an almost complete and irreversible loss at birth. A number of experimental studies were carried out and basically corroborated the conclusions drawn from the above studies [24][25][26][27][28][29]. An important piece of understanding was added by Bouchard and Paek who independently produced evidence (using the fetal sheep model originally described by Meuli et al) that a kind of ''Chiari-malformation'' with hindbrain herniation and hydrocephalus formation can be induced when a cerebrospinal fluid leak is created within the lumbar MMC lesion and that this process is reversible upon in utero coverage of the lesion [30,31].…”

Section: Introductionsupporting

confidence: 65%

Fetal surgery for myelomeningocele is effective: a critical look at the whys

Meuli

Moehrlen

2014

Pediatr Surg Int

View full text Add to dashboard Cite

Formerly, the disastrous cluster of neurologic deficits and associated neurogenic problems in patients with myelomeningocele (MMC) was generally thought to solely result from the primary malformation, i.e., failure of neurulation. Today, however, there is no doubt that a dimensional additional pathogenic mechanism exists. Most likely, it contributes much more to loss of neurologic function than non-neurulation does. Today, there is a large body of compelling experimental and clinical evidence confirming that the exposed part of the non-neurulated spinal cord is progressively destroyed during gestation, particularly so in the third trimester. These considerations gave rise to the two-hit-pathogenesis of MMC with non-neurulation being the first and consecutive in utero acquired neural tissue destruction being the second hit. This novel pathophysiologic understanding has obviously triggered the question whether the serious and irreversible functional loss caused by the second hit could not be prevented or, at least, significantly alleviated by timely protecting the exposed spinal cord segments, i.e., by early in utero repair of the MMC lesion. Based on this intriguing hypothesis and the above-mentioned data, human fetal surgery for MMC was born in the late nineties of the last century and has made its way to become a novel standard of care, particularly after the so-called "MOMS Trial". This trial, published in the New England Journal of Medicine, has indisputably shown that overall, open prenatal repair is distinctly better than postnatal care alone. Finally, a number of important other topics deserve being mentioned, including the necessity to work on the up till now immature endoscopic fetal repair technique and the need for concentration of these extremely challenging cases to a small number of really qualified fetal surgery centers worldwide. In conclusion, despite the fact that in utero repair of MMC is not a complete cure and not free of risk for both mother and fetus, current data clearly demonstrate that open fetal-maternal surgery is to be recommended as novel standard of care when pregnancy is to be continued and when respective criteria for the intervention before birth are met. Undoubtedly, it is imperative to inform expecting mothers about the option of prenatal surgery once their fetus is diagnosed with open spina bifida.

show abstract

“…Previous reports suggested that Tubulin-βIII expression in the bladder muscular layer was reduced by RA exposure and restored at E17 by in utero repair using a chitosan-gelatin membrane patch [23][24][25]. In the present study, both RA and RA + hAFSC bladders had well-organized smooth muscle bundles and there were no differences in α-SMA expression patterns between the two group (Supporting Information Fig.…”

Section: Hafscs-treatment Reduces Neuronal Damage In the Muscular Laysupporting

confidence: 59%

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

Abe

Ochiai

Masuda

et al. 2019

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Despite the poor prognosis associated with myelomeningocele (MMC), the options for prenatal treatments are still limited. Recently, fetal cellular therapy has become a new option for treating birth defects, although the therapeutic effects and mechanisms associated with such treatments remain unclear. The use of human amniotic fluid stem cells (hAFSCs) is ideal with respect to immunoreactivity and cell propagation. The prenatal diagnosis of MMC during early stages of pregnancy could allow for the ex vivo proliferation and modulation of autologous hAFSCs for use in utero stem cell therapy. Therefore, we investigated the therapeutic effects and mechanisms of hAFSCs‐based treatment for fetal MMC. hAFSCs were isolated as CD117‐positive cells from the amniotic fluid of 15‐ to 17‐week pregnant women who underwent amniocentesis for prenatal diagnosis and consented to this study. Rat dams were exposed to retinoic acid to induce fetal MMC and were subsequently injected with hAFSCs in each amniotic cavity. We measured the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion. The exposed spinal area of the hAFSC‐treated group was significantly smaller than that of the control group. Immunohistochemical analysis demonstrated a reduction in neuronal damage such as neurodegeneration and astrogliosis in the hAFSC‐treated group. Additionally, in lesions of the hAFSC‐treated group, HGF expression was upregulated and HGF‐positive hAFSCs were identified, suggesting that these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis. Therefore, in utero hAFSC therapy could become a novel strategy for fetal MMC. Stem Cells Translational Medicine 2019;8:1170–1179

show abstract

Morphology of nervous lesion in the spinal cord and bladder of fetal rats with myelomeningocele at different gestational age

Cited by 14 publications

References 23 publications

In utero repair of fetal rat myelomeningocele affects neuromuscular development in the bladder

In utero repair of fetal rat myelomeningocele affects neuromuscular development in the bladder

Fetal surgery for myelomeningocele is effective: a critical look at the whys

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

Contact Info

Product

Resources

About