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Synthetic tissues offer alternative to animal testing

A team of MRC Harwell researchers will be returning to STFC’s Central Laser Facility (CLF) in the autumn to investigate the properties of their innovative synthetic tissues. The synthetic tissues, which comprise of naturally occurring living cells and artificial hydrogel constituents, reproduce the properties and function of living tissues paving the way for a new approach to testing drug candidates for the treatment of metabolic diseases such as diabetes.

The synthetic tissues attempt to imitate fat tissue, known as white adipose tissues. Despite its negative connotations, fat is an essential organ that stores energy and secretes hormones essential for the regulation of a healthy metabolism. In drug trials, as an alternative to using live animals (such as mice), researchers will often use 2D cell culture models of adipose tissues in which fat cells are encouraged to grow side by side on a flat surface. But these 2D tissues can sometimes fall short in comparison with living tissue due to their structure being insufficiently complex.

As a response to this, researchers Dr Alexander Graham and Dr Rajesh Pandey are developing three-dimensional synthetic tissues that promise to bridge the gap between the two approaches by being both cheap and an effective simulator of biological systems. However, cells cultured in 3D scaffolds are prone to migrating and may distribute unevenly or vacate the scaffold, hindering the successful development of the synthetic tissues. This means that it is a major challenge to create synthetic tissues that retain their shape while replicating the phenotype, architecture and function of the tissue to be modelled.

Dr. Graham and Dr. Pandey worked collaboratively with a spinout company from the University of Oxford and the MRC Harwell Institute respectively to tackle this problem by developing an adipose model that can retain its structure for weeks.

To create their adipose tissue models, the team used fat cells from mice and enclosed them in a droplet of hydrogel that contained selected proteins. These droplets, or spheroids, were then transferred to culture medium and left to mature into fat-laden cells, which were then constructed into three-dimensional models. The question is whether the 3D synthetic models developed and organised fat stores as they would within a living subject and whether they functioned like adipose tissues.

In order to move the development forward, the team needs to compare their 3D synthetic tissue models against the 2D models currently used for drug screening. Unfortunately, gaining the high-quality images required to understand the structure, morphology and properties of the models is beyond the reach of conventional imaging techniques, which can either damage the samples or are unable to produce the high level of resolution required.

STFC’s Central Laser Facility’s  Octopus imaging cluster is ideal for their work because the facility uses a wide-range of multicolour laser-light sources that allows scientists to look at structures as small as a single molecule. The team first used Octopus last year through the Bridging for Innovators (B4i) scheme and were able to obtain some very informative images that would help with the next stage of the product’s development. This autumn, the team will be returning to do more experiments using Octopus.

As well as benefiting from access to CLF’s imaging facilities, the team has also secured funding through STFC’s Harwell Campus’ HealthTec cluster, which has provided Proof of Concept funding for the next stage of work at CLF.  The approaching experiments will use Octopus to investigate the 3D fat spheroids to see how their fat storage abilities respond to being fed nutrients and being exposed to anti-diabetic drugs.

“We have developed a robust 3D model of white adipose tissue which has been shown to be responsive to anti-diabetic drugs,” Dr. Alex Graham said about the research. “It is a powerful platform for potentially identifying new therapeutic interventions for metabolic diseases. This achievement has only been possible through a multi-institutional collaboration between a broad range of specialists from commercial organisations, MRC Harwell Institute and the Central Laser Facility.”

Last updated: 07 October 2019

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