Response differences of HepG2 and Primary Mouse Hepatocytes to morphological changes in electrospun PCL scaffolds

Thomas S R Bate,Anthony Callanan,Stuart J Forbes,Victoria L Gadd

doi:10.1038/s41598-021-81761-z

Thomas S R Bate, Anthony Callanan + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-81761-z

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Abstract

Liver disease cases are rapidly expanding across the globe and the only effective cure for end-stage disease is a transplant. Transplant procedures are costly and current supply of donor livers does not satisfy demand. Potential drug treatments and regenerative therapies that are being developed to tackle these pressing issues require effective in-vitro culture platforms. Electrospun scaffolds provide bio-mimetic structures upon which cells are cultured to regulate function in-vitro. This study aims to shed light on the effects of electrospun PCL morphology on the culture of an immortalised hepatic cell line and mouse primary hepatocytes. Each cell type was cultured on large 4–5 µm fibres and small 1–2 µm fibres with random, aligned and highly porous cryogenically spun configurations. Cell attachment, proliferation, morphology and functional protein and gene expression was analysed. Results show that fibre morphology has a measurable influence on cellular morphology and function, with the alteration of key functional markers such as CYP1A2 expression.

Highlights

Liver disease cases are rapidly expanding across the globe and the only effective cure for end-stage disease is a transplant
Other research is focused on regenerative therapies through the use of stem cells or macrophages and extra-cellular matrix (ECM) scaffolding technologies to remove or reverse the currently irreversible results of liver cirrhosis[7,8,9,10,11]
These effects have been demonstrated through studies focused on stem cells, and are known to translate over to fully differentiated somatic cell types

Summary

Introduction

Liver disease cases are rapidly expanding across the globe and the only effective cure for end-stage disease is a transplant. Other research is focused on regenerative therapies through the use of stem cells or macrophages and extra-cellular matrix (ECM) scaffolding technologies to remove or reverse the currently irreversible results of liver cirrhosis[7,8,9,10,11]. These methods imply the utilisation of in-vitro methods which are in need of re-development and re-engineering to match in-vivo biological complexity and deliver effective platforms for expansion of regenerative cells and invitro drug testing m odels[11,12,13]. Consideration of the mechanical properties of 3D scaffold technologies and how this regulates cell function is essential to the design of in-vitro systems

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