Innovation at CITER

Cardiff Institute for Tissue Engineering and Repair, created in 1993, is a network of scientists principally within Cardiff University. Interests and expertise include basic, translational and clinical research in stem cell science, tissue engineering and repair, and disease translation. Within these broader remits, the research interest of individual colleagues is diverse.

CITER embraces translational research that is conducive to commercial exploitation and encourages partnership with the industry. A core strength is its network expertise enabling it to address complex problems, accessing skill from different disciplines.

To support the network, CITER organises several workshops, seminars and conferences throughout the year, encouraging and fostering new research collaborations, and promoting expertise to external researchers and stakeholders. Industrial partners are encouraged to attend and showcase collaborative works and solutions tailored for researchers. CITER is particularly supportive of early career scientists with financial packages and organisational experience.

CITER also recognises the importance of communication with the public, so supports public events and engages with primary and secondary school children through a number of different activities.

The use of academic knowledge, technology, skills and innovation by industrial partners has been highly successful for improving competitiveness and productivity in Wales and in the UK. CITER is fully supportive of such partnerships and aims to promote academic-industry networking though its activities. Here are some examples of projects carried out by CITER members.

Driving Therapeutic Antibodies and Nanoparticles into Cancer Cells

A Cardiff University team at the School of Pharmacy and Pharmaceutical Sciences and the School of Biosciences at Cardiff University, led by Professor Arwyn T. Jones, has made significant inroads to delivering therapeutic molecules to cancer cells by targeting receptors on their cell surface.

They have identified how strategic targeting and clustering of plasma membrane receptors on cancer cells leads to their internalisation by endocytosis and intracellular degradation. This was particularly prominent with the clinically approved Herceptin (trastuzumab) antibody whose target, HER2, is usually resistant to internalisation and a represents a major driver of cell growth and division in some breast cancer types.

The work, published in late 2015, resulted in further national, international and industrial collaborations, leading to recent publications describing studies on nanoparticles decorated with cancer targeting ligands. With the University of Padova in Italy, they demonstrated how pH responsive nanoparticles, decorated with folic acid, target and enter cancer cells that overexpress the folic acid receptor. Working with polymer chemists at Nottingham University, they showed how thermoresponsive polymer nanoparticles drive endocytosis in a temperature dependant manner.

The Arwyn Jones group has also been working with Astra Zeneca exploring the use of lipid nanoparticles as vectors for the delivery of messenger RNA as therapeutics. The work was published with a front cover image as Sayers et al in Molecular Therapy in late 2019, and Pharmacy PDRA Dr Edd Sayers won a poster prize for his work at the nanoDDS 2019 symposium at MIT Boston USA.

The overall objectives are now to use this new knowledge and tools in order to more efficiently use drug delivery targeting systems such as antibodies (as Antibody Drug Conjugates) and targeted nanoparticles to cells with concomitant delivery of therapeutic small molecule drugs or biomedicines such as peptides, proteins and nucleotides. Further information on this work and publications can be found at www.cardiff.ac.uk/people/view/90846jones-arwyn-tomos. Human induced pluripotent stem (iPS) cells and the formation of eye-like tissue

Scientists at Cardiff University, led by Professor Andrew Quantock, are collaborating with researchers at Osaka University in Japan, headed by Professors Kohji Nishida and Ryuhei Hayashi, to investigate how human induced pluripotent stem (iPS) cells differentiate into cells that resemble those in different tissues of the eye, such as cornea, retina, and lens. The aim is to understand the fundamental mechanisms that drive human eye development, and to work towards iPS cellderived materials for ophthalmic surgery to treat vision loss. The research builds on collaborative work published a few years ago, which showed that a functional corneal epithelium could be fashioned from human iPS cells. This led to Professor Nishida announcing in 2019 that a Japanese woman in her forties had become the first person in the world to have her cornea repaired using iPS cells. Since that time additional surgeries have been carried out in Osaka, confirming the success of this therapeutic approach.

The Cardiff-Osaka collaboration continues apace. With BBSRC funding, Dr Jodie Harrington is working in Osaka with Professor Ryuhei Hayashi and with Drs Jim Ralphs, Justyn Regini and Rob Young in Cardiff to study lens generation from iPS cells; Fight-for-Sight PhD student, Mr Sean Ashworth, with Professor Clare Hughes is investigating how extracellular matrix drives iPS cell differentiation; and Dr Laura Howard, funded by BBSRC, works with Professor Derek Blake and Dr Matt Hill probing the genomic basis of iPS cells forming eye-like tissue.