The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells

Capková, Nikola; Pospíšilová, Veronika; Fedorová, Veronika; Raška, Jan; Pospíšilová, Kateřina; Dal Ben, Matteo; Dvořák, Aleš; Viktorová, Jitka; Bohačiaková, Dáša; Vítek, Libor

doi:10.3390/antiox10101532

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The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells

^1,†,

^2,†,

²,

²,

¹,

³,

^2,4

and

Libor Vítek

^1,5,*

Institute of Medical Biochemistry and Laboratory Diagnostics, Faculty General Hospital and 1st Faculty of Medicine, Charles University, 110 00 Prague, Czech Republic

Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 601 77 Brno, Czech Republic

Department of Biochemistry and Microbiology, University of Chemistry and Technology, 166 28 Prague, Czech Republic

⁴

International Clinical Research Center (ICRC), St. Anne’s University Hospital, 656 91 Brno, Czech Republic

⁵

4th Department of Internal Medicine, Faculty General Hospital and 1st Faculty of Medicine, Charles University, 110 00 Prague, Czech Republic

Author to whom correspondence should be addressed.

^†

Both authors contributed equally.

Academic Editor: Peter L. Oliver

Antioxidants 2021, 10(10), 1532; https://doi.org/10.3390/antiox10101532

Received: 27 August 2021 / Revised: 18 September 2021 / Accepted: 22 September 2021 / Published: 27 September 2021

(This article belongs to the Special Issue Bilirubin and Oxidative Stress)

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Abstract

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 µmol/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 (β-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. View Full-Text

Keywords: bilirubin; neurodevelopment; phototherapy

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Capková, N.; Pospíšilová, V.; Fedorová, V.; Raška, J.; Pospíšilová, K.; Dal Ben, M.; Dvořák, A.; Viktorová, J.; Bohačiaková, D.; Vítek, L. The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells. Antioxidants 2021, 10, 1532. https://doi.org/10.3390/antiox10101532

AMA Style

Capková N, Pospíšilová V, Fedorová V, Raška J, Pospíšilová K, Dal Ben M, Dvořák A, Viktorová J, Bohačiaková D, Vítek L. The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells. Antioxidants. 2021; 10(10):1532. https://doi.org/10.3390/antiox10101532

Chicago/Turabian Style

Capková, Nikola, Veronika Pospíšilová, Veronika Fedorová, Jan Raška, Kateřina Pospíšilová, Matteo Dal Ben, Aleš Dvořák, Jitka Viktorová, Dáša Bohačiaková, and Libor Vítek. 2021. "The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells" Antioxidants 10, no. 10: 1532. https://doi.org/10.3390/antiox10101532

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