Liquid marble technology to create cost-effective 3D cardiospheres as a platform for in vitro drug testing and disease modelling

Abstract

Three-dimensional (3D) cell culturing has several advantages over 2D cultures. 3D cell cultures more accurately mimic the in vivo environment, which is vital to obtain reliable results in disease modelling and toxicity testing. With the introduction of the Yamanaka factors, reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) became available. This iPSC technology provides a scalable source of differentiated cells. iPSCs can be programmed to differentiate into any cell type of the body, including cardiomyocytes. These heart-specific muscle cells, can then serve as a model for therapeutic drug screening or assay development. Current methods to achieve multicellular spheroids by 3D cell cultures, such as hanging drop and spinner flasks are expensive, time-consuming and require specialized materials and training. Hydrophobic powders can be used to create a micro environment for cell cultures, which are termed liquid marbles (LM). In this procedure we describe the first use of the LM technology for 3D culturing in vitro derived human cardiomyocytes which results in the formation of cardiospheres within 24h. The cardiospheres could be used for several in depth and high-throughput analyses.

Liquid marble – a high-yield micro-photobioreactor platform

“…38 Previous studies also reported the feasibility of observing reactions and processes taking place in liquid marbles. 41 The porous shell of a liquid marble enables gas to diffuse across the coating layer and into the core liquid. [42][43][44][45] Previous studies demonstrated the use of a liquid marble as a gas sensor.…”

Drycells: Cell‐Suspension Micro Liquid Marbles for Single‐Cell Picking

“…[15,16] In addition, cell culturing using a liquid marble, which enables the formation of cell aggregates such as spheroids in millimetric droplets, has recently been reported. [17][18][19][20] In the context of single-cell analysis, a liquid marble can be potentially reduced to cell size for isolating single and multiple cells. The challenge here is the formation of stable micrometersized liquid marbles, which is yet to be realized because of the specifics of the liquid-marble formation process.…”

“…[ 15,16 ] In addition, cell culturing using a liquid marble, which enables the formation of cell aggregates such as spheroids in millimetric droplets, has recently been reported. [ 17–20 ]…”

Stearate Liquid Marbles for Bacterial Cellulose Production: Influence of the Liquid Marble Interface on Bacterial Cellulose Properties

“…Owing to these advantages, LMs have great potential in various applications, such as gas sensing, blood typing, lab-on-chip devices for genetic engineering, and manipulation and transport of minute quantities of liquids in microfluidic systems . In particular, gas and vapor transport into or out of LMs makes them ideal chemical reactors for gas–liquid reactions and cultivation media for aerobic microorganisms. , Recently, LMs have been deployed as CO 2 capture particles and cell cultivation media. − …”