Organic semiconductors are constantly gaining interest in regenerative medicine. Their tunable physico-chemical properties, including electrical conductivity, are very promising for the control of stem-cell differentiation. However, their use for combined material-based and electrical stimulation remains largely underexplored. Therefore, we carried out a study on whether a platform based on the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) can be beneficial to the differentiation of mouse embryonic stem cells (mESCs). The platform was prepared using the layout of a standard 24-well cell-culture plate. Polyethylene naphthalate foil served as the substrate for the preparation of interdigitated gold electrodes by physical vapor deposition. The PEDOT:PSS pattern was fabricated by precise screen printing over the gold electrodes. The PEDOT:PSS platform was able to produce higher electrical current with the pulsed-direct-current (DC) electrostimulation mode (1 Hz, 200 mV/mm, 100 ms pulse duration) compared to plain gold electrodes. There was a dominant capacitive component. In proof-of-concept experiments, mESCs were able to respond to such electrostimulation by membrane depolarization and elevation of cytosolic calcium. Further, the PEDOT:PSS platform was able to upregulate cardiomyogenesis and potentially inhibit early neurogenesis per se with minor contribution of electrostimulation. Hence, the present work highlights the large potential of PEDOT:PSS in regenerative medicine.

• Keywords
• PEDOT:PSS, conductive polymer, electrostimulation, embryonic stem cells, screen print,
• MeSH
• Bridged Bicyclo Compounds, Heterocyclic chemistry   MeSH
• Cell Differentiation * MeSH
• Cell Culture Techniques MeSH
• Electric Conductivity * MeSH
• Electrodes MeSH
• Mouse Embryonic Stem Cells cytology   drug effects   MeSH
• Mice MeSH
• Polymers chemistry   pharmacology   MeSH
• Polystyrenes chemistry   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bridged Bicyclo Compounds, Heterocyclic MeSH
• poly(3,4-ethylene dioxythiophene) MeSH Browser
• Polymers MeSH
• polystyrene sulfonic acid MeSH Browser
• Polystyrenes MeSH

Nitro-oleic acid (NO2-OA), pluripotent cell-signaling mediator, was recently described as a modulator of the signal transducer and activator of transcription 3 (STAT3) activity. In our study, we discovered new aspects of NO2-OA involvement in the regulation of stem cell pluripotency and differentiation. Murine embryonic stem cells (mESC) or mESC-derived embryoid bodies (EBs) were exposed to NO2-OA or oleic acid (OA) for selected time periods. Our results showed that NO2-OA but not OA caused the loss of pluripotency of mESC cultivated in leukemia inhibitory factor (LIF) rich medium via the decrease of pluripotency markers (NANOG, sex-determining region Y-box 1 transcription factor (SOX2), and octamer-binding transcription factor 4 (OCT4)). The effects of NO2-OA on mESC correlated with reduced phosphorylation of STAT3. Subsequent differentiation led to an increase of the ectodermal marker orthodenticle homolog 2 (Otx2). Similarly, treatment of mESC-derived EBs by NO2-OA resulted in the up-regulation of both neural markers Nestin and β-Tubulin class III (Tubb3). Interestingly, the expression of cardiac-specific genes and beating of EBs were significantly decreased. In conclusion, NO2-OA is able to modulate pluripotency of mESC via the regulation of STAT3 phosphorylation. Further, it attenuates cardiac differentiation on the one hand, and on the other hand, it directs mESC into neural fate.

• Keywords
• STAT3, cardiomyogenesis, mouse embryonic stem cells, neurogenesis, nitro-oleic acid, pluripotency,
• MeSH
• Biomarkers metabolism   MeSH
• Cell Differentiation * drug effects   MeSH
• Nitro Compounds pharmacology   MeSH
• Embryoid Bodies drug effects   metabolism   MeSH
• Myocytes, Cardiac drug effects   metabolism   MeSH
• Oleic Acids pharmacology   MeSH
• Mouse Embryonic Stem Cells cytology   drug effects   metabolism   MeSH
• Mice MeSH
• Neurons cytology   drug effects   metabolism   MeSH
• Organogenesis drug effects   MeSH
• Pluripotent Stem Cells drug effects   metabolism   MeSH
• Signal Transduction drug effects   MeSH
• STAT3 Transcription Factor metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• CXA-10 MeSH Browser
• Nitro Compounds MeSH
• Oleic Acids MeSH
• STAT3 Transcription Factor MeSH

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

• Keywords
• biocompatibility, conducting polymer, neurogenesis, polypyrrole, stem cells,
• MeSH
• Cell Differentiation drug effects   genetics   MeSH
• Cell Line MeSH
• Embryoid Bodies cytology   drug effects   MeSH
• Gene Expression drug effects   MeSH
• Molecular Structure MeSH
• Mouse Embryonic Stem Cells cytology   drug effects   metabolism   MeSH
• Mice MeSH
• Neural Stem Cells cytology   drug effects   metabolism   MeSH
• Neurogenesis drug effects   genetics   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Polymers chemistry   pharmacology   MeSH
• Pyrroles chemistry   pharmacology   MeSH
• PAX6 Transcription Factor genetics   MeSH
• Basic Helix-Loop-Helix Transcription Factors genetics   MeSH
• SOXB1 Transcription Factors genetics   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Ascl1 protein, mouse MeSH Browser
• Polymers MeSH
• polypyrrole MeSH Browser
• Pyrroles MeSH
• PAX6 Transcription Factor MeSH
• Basic Helix-Loop-Helix Transcription Factors MeSH
• SOXB1 Transcription Factors MeSH