Development of a DsRed-expressing HepaRG cell line for real-time monitoring of hepatocyte-like cell differentiation by fluorescence imaging, with application in screening of novel geometric microstructured cell growth substrates.

The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cells. Cell treatment with specific differentiation inducers results in a mixture of hepatocyte- and biliary-like cells, accompanied by upregulation of liver-specific proteins, drug metabolizing enzymes, tr...

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Publicado en:Biomedical Microdevices Vol. 19; no. 1; pp. 1 - 10
Autores principales: Uta, Mihaela, Sima, Livia, Hoffmann, Patrik, Dinca, Valentina, Branza-Nichita, Norica
Formato: Journal Article
Publicado: Springer Nature Mar2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2017
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s10544-016-0146-z
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        atl: Development of a DsRed-expressing HepaRG cell line for real-time monitoring of hepatocyte-like cell differentiation by fluorescence imaging, with application in screening of novel geometric microstructured cell growth substrates.
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        au:
          Uta, Mihaela
          Sima, Livia
          Hoffmann, Patrik
          Dinca, Valentina
          Branza-Nichita, Norica
        affil: Department of Viral Glycoproteins , Institute of Biochemistry of the Romanian Academy , Splaiul Independentei 296, Sector 6 Bucharest Romania
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      ab: The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cells. Cell treatment with specific differentiation inducers results in a mixture of hepatocyte- and biliary-like cells, accompanied by upregulation of liver-specific proteins, drug metabolizing enzymes, transcription regulators, membrane receptors or innate immune response effectors. These features make the HepaRG cells a suitable and handy replacement for primary hepatocytes, to study hepatic functions in vitro. However, cell differentiation is a long, variable process, requiring special culture conditions, while the resulting mixed cell populations is usually a major drawback. This process can potentially be controlled by interface characteristics, such as substrate topography. To screen for such novel substrates, we have first developed a new HepaRG cell line, designated as HepaRG, expressing the reporter gene DsRed. The fluorescent protein was expressed in hepatocyte- and not biliary-like cells, in a differentiation dependent-manner. We have further used replicated microstructured gradients of polydimethylsiloxane (PDMS) that allow three-dimensional manipulation in vitro, to monitor HepaRG differentiation in real time. We demonstrate that this approach enables the controlled assembly of viable hepatocyte-like cells for functional studies, which can be maintained in culture without loss of differentiation. The regulated expression of the DsRed reporter proved a valuable tool not only for rapid screening of novel cell growth substrates favoring cell differentiation, but also, to enrich the hepatocyte-like cell population by fluorescence-activated cell sorting to investigate liver-specific processes in vitro.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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