Publication details
The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells
| Authors | |
|---|---|
| Year of publication | 2021 |
| Type | Article in Periodical |
| Magazine / Source | Antioxidants |
| MU Faculty or unit | |
| Citation | CAPKOVA, Nikola, Veronika POSPÍŠILOVÁ, Veronika FEDOROVÁ, Jan RAŠKA, Katerina POSPISILOVA, Matteo DAL BEN, Ales DVORAK, Jitka VIKTOROVA, Dáša BOHAČIAKOVÁ and Libor VITEK. The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells. Antioxidants. Basel: MDPI, 2021, vol. 10, No 10, p. 1-16. ISSN 2076-3921. Available from: https://dx.doi.org/10.3390/antiox10101532. |
| web | https://www.mdpi.com/2076-3921/10/10/1532 |
| Doi | http://dx.doi.org/10.3390/antiox10101532 |
| Keywords | bilirubin; neurodevelopment; phototherapy |
| Description | The 'gold standard' treatment of severe neonatal jaundice is phototherapy with blue-green light, which produces more polar photo-oxidation products that are easily excreted via the bile or urine. The aim of this study was to compare the effects of bilirubin (BR) and its major photo-oxidation product lumirubin (LR) on the proliferation, differentiation, morphology, and specific gene and protein expressions of self-renewing human pluripotent stem cell-derived neural stem cells (NSC). Neither BR nor LR in biologically relevant concentrations (12.5 and 25 mu mol/L) affected cell proliferation or the cell cycle phases of NSC. Although none of these pigments affected terminal differentiation to neurons and astrocytes, when compared to LR, BR exerted a dose-dependent cytotoxicity on self-renewing NSC. In contrast, LR had a substantial effect on the morphology of the NSC, inducing them to form highly polar rosette-like structures associated with the redistribution of specific cellular proteins (beta-catenin/N-cadherin) responsible for membrane polarity. This observation was accompanied by lower expressions of NSC-specific proteins (such as SOX1, NR2F2, or PAX6) together with the upregulation of phospho-ERK. Collectively, the data indicated that both BR and LR affect early human neurodevelopment in vitro, which may have clinical relevance in phototherapy-treated hyperbilirubinemic neonates. |
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