Clusters of amniotic fluid cells and their associated early neuroepithelial markers in experimental myelomeningocele: Correlation with astrogliosis

PLoS ONE, 2017 · DOI: https://doi.org/10.1371/journal.pone.0174625 · Published: March 30, 2017

Simple Explanation

This study examined the cells found in the amniotic fluid of rat fetuses with myelomeningocele (MMC), a severe birth defect where the spinal cord is exposed. The researchers looked for a link between these cells and the abnormal development of MMC. They discovered that cells from the amniotic fluid of MMC fetuses formed clusters in culture that were not seen in normal fetuses. These clusters contained cells with markers of early brain and spinal cord development. The appearance of these cell clusters correlated with the activation of astrocytes (a type of brain cell) in the injured spinal cord of the MMC fetuses, suggesting a relationship between the cells in the amniotic fluid and the severity of the spinal cord damage.

Study Duration

Not specified

Participants

38 Sprague-Dawley pregnant rats (30 with retinoic acid, 8 with olive oil)

Evidence Level

Not specified

Key Findings

1
A population of cells from the amniotic fluid of MMC fetuses (MMC-AF) formed adherent clusters of tightly packed cells, which were absent from the AF of normal control fetuses (norm-AF).
2
MMC-AF clusters contained cells co-expressing adherens junction associated proteins (ZO-1), N-cadherin and F-actin at sites of cell-cell contacts, along with markers of early neuroepithelial cells such as SOX-1 and Pax-6, and stem/progenitor cell markers such as SOX-2 and nestin.
3
The appearance of cluster forming cells in cultures from MMC-AF correlated with activation of astrogliosis associated with the spinal cord injury in MMC fetuses.

Research Summary

The study identified clusters of adherent cells in short-term cultures from amniotic fluid cells of MMC-AF samples, which were phenotypically reminiscent of early neuroepithelium and absent in norm-AF samples. Cells in MMC-AF clusters co-expressed adherens junction proteins ZO-1 and N-cadherin, contributing to cell-cell adhesion, and markers of early neuroepithelial cells (SOX-1 and Pax-6) along with neural stem/progenitor cell markers (SOX-2 and nestin). The appearance of MMC-AF clusters in cultures was related to the pathology of MMC, specifically astrogliosis, in the exposed spinal cord of age-matched fetuses, suggesting the cells may be a sensitive indicator of spinal cord damage during MMC development.

Practical Implications

Prenatal Diagnosis

The presence of these unique cluster-forming neuroepithelial cells in amniotic fluid may serve as a diagnostic marker for the severity of spinal cord pathology in MMC fetuses.

Therapeutic Monitoring

The absence of these cells in the amniotic fluid of treated fetuses could potentially serve as an indicator of therapeutic success in prenatal interventions for MMC.

In Vitro Disease Modeling

MMC-AF clusters may serve as a valuable in vitro model for studying the mechanisms of MMC development and spinal cord injury, aiding in the development of novel regenerative strategies.

Study Limitations

1
The phenotype of isolated cells could have been affected by the exposure to culture media.
2
Analysis of cells from fresh AF specimens using flow cytometry would overcome these limitations.
3
Quantitative analysis of these cells from fresh AF specimens by flow cytometry should help to further elucidate the relationship between the severity of MMC and changes in the cellular content of AF at different time points during gestation.

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