Acellular Approaches for Therapeutic Delivery: UK Regenerative Medicine Platform Hub Application

Regenerative medicine will transform human health over the next 30 years. We have the ability to create new treatments that repair damaged tissues and restore the body to its original health. Our Hub will play a role in the development of these treatments and thereby help to build a strong UK industry that makes a worldwide impact. We are particularly interested in the methods by which these new treatments are administered to patients. It is difficult to deliver a living cell as a medicine because these cells are fragile and will not form tissue if they experience adverse conditions. We will invent methods to deliver cells to the correct part of the body in an optimal state to repair tissue. Our Hub will create new materials and technologies that can be used in a very large number of future medical applications. In the first phase of our work we will design new materials that recreate the opitmal conditions for stem cells to form tissue. Next we will work with 7 teams who are directly involved in translating new scientific breakthroughs into new medicines. These teams will test our materials and help improve their design by initial studies of suitability for use in Parkinson's Disease, liver diseases, bone repair, skin wound regeneration, cartilage repair, treatments of oesophageal cancer and to assist in anterior cruciate ligament operations.

We are working with leading UK industry to ensure that our technologies can be taken forward as new products that originate in the UK but treat patients across the World.

Our Hub is concerned with the problem of how a cell or drug therapy for regenerative medicine can arrive at the site of action in an optimal state for rapid and complete tissue formation. Our approach is to design new generations of acellular matrices that create 3D environments that promote tissue formation. We propose that for cell therapies to be efficacious and reliable we must ensure that the cells arrive at the site of action with high viability, minimal physical and biological disruption and with a self-assembling niche that can host, in collaboration with local signals within the patient, spontaneous tissue formation and integration. Overarching scientific principles of these core activities are:

1. The need to mimic hierarchical structures that control cell and tissue behaviour during development and tissue function.

2. Spatial and temporal control of molecular and mechanical stimuli. Tissue morphogenesis and repair use cascades of signalling molecules over periods of hours, days, weeks and months to control cell behaviour. These signals are interpreted by cells in the context of the local mechanical environments and the presence of co-signals (eg integrin mediated cell adhesion).

3.A single cell therapy will encounter numerous changes in environment from manufacture to engraftment. The delivery system should be a chaperone to protect the cell or drug payload against environmental changes.

4. All delivery systems must be able to be translated into clinically and commercially viable products. Therefore, delivery goals should be achieved with the simplest solutions bearing in mind the regulatory process and the risk/benefit of the final product.

During the first 4 years of the Hub we have planned for a range of early impacts across a wide range of beneficiaries. These include:

TSB Cell Therapy Catapult Centre: We will fully support the early development of the Centre by making available technologies and advise. We believe that the Catapult Centre will be very well placed for early clinical adoption and quality control issues but will need to import expertise and technologies for acellular delivery systems. We will invite the Catapult Centre to be part of our International Steering Committee and will aim to meet at least quarterly with the Centre to explore opportunities.

UK Industry: We have strong industry involvement from day 1 of our Hub and indeed this reflects the fact that all our Hub groups have collaborated with industry for many years. We will communicate openly with all industry and invite new companies into the Hub. IP discussions will need to be undertaken under CDAs. Our Open Conferences will offer new opportunities for companies to get involved and exchange ideas with other companies, clinicians and academics. We will aim to begin the translation of our technologies within the first 4 years of the Hub to enhance future regenerative medicine products

NHS and Clinicians: Our Hub and Spoke model will create opportunities for early clinical translation. Within the first 4 years we expect our first generation acellular technologies (i.e. the systems we developed before the Hub was created) to be integrated into clinical trials. Lead opportunities include anterior cruciate ligament repair and integration into bone with Newcastle and the use of GMP produced human mesenchymal stem cells in autoimmune liver diseases.

General Public and Schools: The outreach programme that we describe in our main proposal will make an impact within the first 4 years on the understanding of regenerative medicine. Using the Royal Society Summer Exhibition (subject to application) and other mechanisms that we have been committed to for many years we will engage with general public to explain, without inappropriately raising expectation, the clinical and commercial potential of the field. We believe that regenerative medicine has a special responsibility to explain science and engineering to Schoolchildren. The field is exciting due to the promise to be the major medical breakthrough of the next 50 years and also exemplifies why biology, chemistry, materials and engineering are so important to their futures. Again our outreach programme ensures impact within 4 years through a Schools programme.

International Community: We want our Hub to be the international centre for delivery systems and acellular technologies and believe that based on our current profile this is a realistic aim. We will engage on an international basis to promote the UK as a centre of excellence in all aspects of regenerative medicine and specifically in the field of our Hub. Our track records show evidence of impact in India (RCUK Science Bridge and Wellcome Trust Affordable Medicines), US (patent licenses), Europe (CE marks, product launches and clinical trials), China (Shanghai Nottingham Advanced Academy and Doctoral training programmes), Japan (joint development of delivery systems) and many others.