La plasticidad del hepatocito y su relevancia en la fisiología y la patología hepática

The liver is one of the most important organs that contribute to maintain metabolic homeostasis in vertebrates, with a high regenerative capacity. Liver is constituted by diverse cellular types, which work together to accomplish the organ function. Hepatocytes are the main cellular type responsible for most of hepatic functions; they are a heterogeneous population with specialized metabolic functions. Several signaling pathways such as TGF-β/Smads, Hippo/YAP-TAZ and Wnt/ β-catenin, among others, regulate hepatocytes phenotype. These cells are normally in a quiescent state but they exhibit plasticity in response to liver damage; thus, they can proliferate or change their phenotype through process such as transdifferentiation or transformation in order to contribute to the maintenance of liver homeostasis or during the development of diverse pathologies.El hígado es uno de los principales órganos encargados de mantener la homeostasis en vertebrados,  además de poseer una gran capacidad regenerativa. El hígado está constituido por diversos tipos celulares que de forma coordinada contribuyen para que el órgano funcione eficientemente. Los hepatocitos representan el tipo celular principal de este órgano y llevan a cabo la mayoría de sus actividades; además, constituyen una población heterogénea de células epiteliales con funciones especializadas en el metabolismo. El fenotipo de los hepatocitos está controlado por diferentes vías de señalización, como la vía del TGFβ/Smads, la ruta Hippo/YAP-TAZ y la vía Wnt/β-catenina, entre otras. Los hepatocitos son células que se encuentran normalmente en un estado quiescente, aunque cuentan con una plasticidad intrínseca que se manifiesta en respuesta a diversos daños en el hígado; así, estas células reactivan su capacidad proliferativa o cambian su fenotipo a través de procesos celulares como la transdiferenciación o la transformación, para contribuir a mantener la homeostasis del órgano en condiciones saludables o desarrollar diversas  patologías

Fabrication of low-cost micropatterned polydimethyl-siloxane scaffolds to organise cells in a variety of two-dimensioanl biomimetic arrangements for lab-on-chip culture platforms

We present the rapid-prototyping of type I collagen micropatterns on poly-dimethylsiloxane substrates for the biomimetic confinement of cells using the combination of a surface oxidation treatment and 3-aminopropyl triethoxysilane silanisation followed by glutaraldehyde crosslinking. The aim of surface treatment is to stabilise microcontact printing transfer of this natural extracellular matrix protein that usually wears out easily from poly-dimethylsiloxane, which is not suitable for biomimetic cell culture platforms and lab-on-chip applications. A low-cost CD-DVD laser was used to etch biomimetic micropatterns into acrylic sheets that were in turn replicated to poly-dimethylsiloxane slabs with the desired features. These stamps were finally inked with type I collagen for microcontact printing transfer on the culture substrates in a simple manner. Human hepatoma cells (HepG2) and rat primary hepatocytes, which do not adhere to bare poly-dimethylsiloxane, were successfully seeded and showed optimal adhesion and survival on simple protein micropatterns with a hepatic cord geometry in order to validate our technique. HepG2 cells also proliferated on the stamps. Soft and stiff poly-dimethylsiloxane layers were also tested to demonstrate that our cost-effective process is compatible with biomimetic organ-on-chip technology integrating tunable stiffness with a potential application to drug testing probes development where such cells are commonly used