Public Funding for Manchester Biogel Limited

Stem cells are a powerful tool in biomedical research and applications, including generation of complex _in vitro_ models, disease modelling, cell therapy and drug discovery. Furthermore, stem cells can differentiate to form different types of cells, tissues and organs and can be grown to mimic diseases such as cancer and other tissue-related disorders. Within the stem cell environment, differentiation is influenced by extracellular matrix components and growth factors, which provide key instructive signals. Of particular interest are their use in generating organoids (mini organs), where clusters of stem cells come together to mimic the native microenvironment of tissues and organs. A motivation for the use of stems cells is their extraordinary potential of changing our understanding of basic biology, and the development of complex preclinical models. They also have the capacity to reduce animal usage in research and development. The growth and differentiation of stem cells in 3-dimensional (3D) have largely been demonstrated with the use of commercially available animal-derived product (3D gel). As well as ethical issues involved in its harvest, this product have significant batch-to-batch variability occurring from inter-individual species and inter-supplier variation. This animal-derived 3D gel also demonstrates thermo-responsive properties, displaying liquid properties at 4oC but forming a gel at room temperature. This significantly impacts how scientists work with it and its translational capacity in high-throughput applications, as these parameters are not compatible with essential high throughput and robotic systems. Most experiments using this product are therefore not reproducible and make data interpretation difficult. To fully understand the differentiation ability of stem cells and develop their capacity to reduce animal usage in research, it is imperative to have a non-animal derived 3D gel that shows consistent batch production, easy to handle properties for better translation in a laboratory or clinical setting. Our PeptiGel(r) products are biologically relevant, synthetic hydrogels that mimic a tissues' cellular environment through having tuneable properties to simulate the natural extracellular matrix of a native tissue. They have been shown to support the growth of a variety of cell types. However robust data of PeptiGels(r) interactions with stem cell populations is lacking. Therefore, the aim of this project is to reproducibly assess and validate PeptiGel(r) products to understand the ideal growth and differentiation environmental conditions for human mesenchymal stem cell culture. The successful completion of this project will drive forward PeptiGel(r) market penetration, further develop solutions for mesenchymal stem cell work and increase revenue.

Organoids are 3-dimensional (3D) clusters of stem cells that come together and emulate the microenvironment within individual organs, whether that be liver, kidney, heart, gut or other specific organs. Essentially, they can be viewed as miniature, simplified organs. They typically range in size from a few micrometers to five millimeters and there are potentially as many different organoids as there are different tissues and organs in the body. Organoids can also be grown that mimic diseased such as cancer and brain disorders. Such a diverse range of organoids can form by controlling the differentiation of the specific stem cell used, which can be influenced by the cells receiving instructive signals from the 3D extracellular matrix (ECM) and its components, such as bioactive proteins, and the medium the organoids grow in. Organoids hold extraordinary promise: they are a truly disruptive technology capable of completely transforming our understanding of basic biology and also revolutionising the drug discovery process, and its reliance on animal models. That said, growing organoids in the laboratory still requires the use of animal-derived components; in particular, the 3D gel matrix in which organoids grow, which is made from mouse tumours. There are very few suppliers of this matrix and because it is made from animals, each batch is slightly different, it is also unusual in that it is liquid at 4oC but sets to a gel at room temperature, this makes it very difficult for scientists to use and not compatible with robotic systems needed in high throughput drug discovery. Thus, to fully develop the potential of organoids in their capacity to reduce the need for use of animals in research, it is essential that a replacement for this type of 3D matrix is obtained, which is not derived from animals. The aim of this project is to develop a new, fully synthetic (non-animal derived) 3D gel matrix which is optimised for the growth of organoids and can be used in the future for industrial-scale organoid production to drive forwards biomedical research, drug discovery and development of new therapeutics. This will be achieved by combining the proprietary synthetic matrix from Manchester BIOGEL with the optimised bioactive cell signalling growth factor proteins from Qkine to create a wholly synthetic hydrogel that recreates the ideal growth environment for the organoids. Cellesce, a specialist organoid company will help tailor the synthetic hydrogels for different organoid types and downstream applications to maximise the impact on science and the commercial potential of the combined technology.