当前位置： SCI文献检索 > Scientific Reports期刊下所有文献 > Tethered primary hepatocyte spheroids on polystyrene multi-well plates for high-throughput drug safety testing.

Tethered primary hepatocyte spheroids on polystyrene multi-well plates for high-throughput drug safety testing.

Abstract：

:Hepatocyte spheroids are useful models for mimicking liver phenotypes in vitro because of their three-dimensionality. However, the lack of a biomaterial platform which allows the facile manipulation of spheroid cultures on a large scale severely limits their application in automated high-throughput drug safety testing. In addition, there is not yet a robust way of controlling spheroid size, homogeneity and integrity during extended culture. This work addresses these bottlenecks to the automation of hepatocyte spheroid culture by tethering 3D hepatocyte spheroids directly onto surface-modified polystyrene (PS) multi-well plates. However, polystyrene surfaces are inert toward functionalization, and this makes the uniform conjugation of bioactive ligands very challenging. Surface modification of polystyrene well plates is achieved herein using a three-step sequence, resulting in a homogeneous distribution of bioactive RGD and galactose ligands required for spheroid tethering and formation. Importantly, treatment of polystyrene tethered spheroids with vehicle and paradigm hepatotoxicant (chlorpromazine) treatment using an automated liquid handling platform shows low signal deviation, intact 3D spheroidal morphology and Z' values above 0.5, and hence confirming their amenability to high-throughput automation. Functional analyses performance (i.e. urea and albumin production, cytochrome P450 activity and induction studies) of the polystyrene tethered spheroids reveal significant improvements over hepatocytes cultured as collagen monolayers. This is the first demonstration of automated hepatotoxicant treatment on functional 3D hepatocyte spheroids tethered directly on polystyrene multi-well plates, and will serve as an important advancement in the application of 3D tethered spheroid models to high throughput drug screening.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Tasnim F,Singh NH,Tan EKF,Xing J,Li H,Hissette S,Manesh S,Fulwood J,Gupta K,Ng CW,Xu S,Hill J,Yu H

doi

10.1038/s41598-020-61699-4

subject

Has Abstract

pub_date

2020-03-16 00:00:00

pages

4768

issue

issn

2045-2322

pii

10.1038/s41598-020-61699-4

journal_volume

pub_type

杂志文章

在线工具

Tethered primary hepatocyte spheroids on polystyrene multi-well plates for high-throughput drug safety testing.