Spheroid culture of primary hepatocytes with short fibers as a predictable in vitro model for drug screening.

Establishment of a reliable in vitro liver models for drug screening remnants challenge with respect to the withdrawal of hepatocyte spheroids growth and adapt to the current high-throughput systems. In this study, short fibers used as a scaffold for the generation of controlled size hepatocyte spheroids that recapitulate in vivo phenotype and function of the heart. Spheroid formation is modulated by the length and galactose / RGD graft of short fibers, and fibers of short length 50 m motivating the formation of spherical with optimal liver function. short fibers distributed throughout the entire round for the withdrawal of hepatocyte growth compact to form spheroids.

Compared to free scaffolding spheroid culture in agarose-coated plates, culture round with short fibers achieve higher clearance level of the drug model and provide a better prediction of in vivo drug clearance rate with 0.886 correlation value.

In addition, the ability of drug metabolism is very sensitive to metabolic enzyme inducers and inhibitors, and responsiveness was maintained for 20 days of culture, showed efficient in vitro models to determine drug-drug interactions. Therefore, cultural round with short fibers provide strategies easily manipulated to maintain hepatocyte function for a long period and allowing ready to be placed in a conventional multiwell plates and a variety of tools organ-on-a-chip for high-throughput drug screening.

Spheroid culture of primary hepatocytes with short fibers as a predictable in vitro model for drug screening.
Spheroid culture of primary hepatocytes with short fibers as a predictable in vitro model for drug screening.

3D Culture System for Liver Tissue Mimicking Hepatic Plates for Improved Human hepatocytes (C3A) Function and Polarity.

3D in vitro hepatocyte culture is a core aspect of liver tissue engineering. However, the conventional 3D culture can not maintain hepatocyte polarity, functional phenotype, or survival. Here, we employ a microfluidic chip technology combined with naturally alginate hydrogel to build a 3D liver tissue mimicking liver dish.

We comprehensively evaluated the survival of cultured hepatocytes, functions, and polarity. transcriptome sequencing was used to analyze changes in hepatocyte polarity pathway. The data show that, with increasing duration of the culture, the viability, function, polarity, mRNA expression, and ultrastructure of liver hepatocytes plate mimetic enhanced 3D.

Furthermore, liver dishes 3D mimetic culture can promote changes in bile secretion pathway through effector mechanisms associated with nuclear receptors, bile uptake and efflux transporters. This study provides a scientific basis and evidence for the physiological structure of the bionic hearts prepared using 3D culture.

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System and liver tissue cultured described here can serve as a better in vitro Platform culture of 3D and basic unit for varied applications, including drug development, research hepatocyte polarity, the design of the bioreactor liver bioartificial, and network and construction of organs for tissue engineering heart or liver cholestasis injury.