Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele
Myelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the backbone and spinal canal do not close completely during early embryonic development. This condition results in serious morbidity and increased mortality after birth. Folic acid significantly reduces, and conversely, f...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/6101609 |
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| author | Vardine Sahakyan Enrico Pozzo Robin Duelen Jan Deprest Maurilio Sampaolesi |
| author_facet | Vardine Sahakyan Enrico Pozzo Robin Duelen Jan Deprest Maurilio Sampaolesi |
| author_sort | Vardine Sahakyan |
| collection | DOAJ |
| description | Myelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the backbone and spinal canal do not close completely during early embryonic development. This condition results in serious morbidity and increased mortality after birth. Folic acid significantly reduces, and conversely, folate antagonist methotrexate (MTX) and valproic acid (VPA) increase the occurrence of NTDs, including MMC. How these pharmacological agents exactly influence the early neurulation process is still largely unclear. Here, we characterized human amniotic fluid-derived stem cells (AFSCs) from prenatally diagnosed MMC and observed an effect of MTX and VPA administration on the early neural differentiation process. We found that MMC-derived AFSCs highly expressed early neural and radial glial genes that were negatively affected by MTX and VPA exposure. In conclusion, we setup a human cell model of MMC to study early neurogenesis and for drug screening purposes. We also proposed the detection of early neural gene expression in AFSCs as an additional MMC diagnostic tool. |
| format | Article |
| id | doaj-art-42576ed90de6411e992b33d7e3206aca |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-42576ed90de6411e992b33d7e3206aca2025-02-03T05:58:06ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/61016096101609Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from MyelomeningoceleVardine Sahakyan0Enrico Pozzo1Robin Duelen2Jan Deprest3Maurilio Sampaolesi4Department of Development and Regeneration, Stem Cell Institute, Stem Cell Biology and Embryology Unit, Translational Cardiomyology Laboratory, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Stem Cell Institute, Stem Cell Biology and Embryology Unit, Translational Cardiomyology Laboratory, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Stem Cell Institute, Stem Cell Biology and Embryology Unit, Translational Cardiomyology Laboratory, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Division Woman and Child, University Hospitals Leuven, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Stem Cell Institute, Stem Cell Biology and Embryology Unit, Translational Cardiomyology Laboratory, KU Leuven, Leuven, BelgiumMyelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the backbone and spinal canal do not close completely during early embryonic development. This condition results in serious morbidity and increased mortality after birth. Folic acid significantly reduces, and conversely, folate antagonist methotrexate (MTX) and valproic acid (VPA) increase the occurrence of NTDs, including MMC. How these pharmacological agents exactly influence the early neurulation process is still largely unclear. Here, we characterized human amniotic fluid-derived stem cells (AFSCs) from prenatally diagnosed MMC and observed an effect of MTX and VPA administration on the early neural differentiation process. We found that MMC-derived AFSCs highly expressed early neural and radial glial genes that were negatively affected by MTX and VPA exposure. In conclusion, we setup a human cell model of MMC to study early neurogenesis and for drug screening purposes. We also proposed the detection of early neural gene expression in AFSCs as an additional MMC diagnostic tool.http://dx.doi.org/10.1155/2017/6101609 |
| spellingShingle | Vardine Sahakyan Enrico Pozzo Robin Duelen Jan Deprest Maurilio Sampaolesi Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele Stem Cells International |
| title | Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele |
| title_full | Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele |
| title_fullStr | Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele |
| title_full_unstemmed | Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele |
| title_short | Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele |
| title_sort | methotrexate and valproic acid affect early neurogenesis of human amniotic fluid stem cells from myelomeningocele |
| url | http://dx.doi.org/10.1155/2017/6101609 |
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