Centre for Innovative Manufacturing in Regenerative Medicine

EPSRC Centre Annual Review

2012-2013

Mission
The EPSRC Centre for Innovative Manufacturing in Regenerative Medicine provides an integrated platform of fundamental and translational research a translational go-to resource for the regenerative medicine product developer. We focus on: Undertaking world-leading research   esting and implementing ideas in clinical T and industrial settings  reating next generation platforms for manufacturing C regenerative medicines Informing business models, policy and public debate  Through a skills base spanning disciplines from biology through to manufacturing science, the EPSRC Centre brings together a critical mass of capacity and capability that can rapidly and proactively address the evolving needs of the regenerative medicine manufacturing industry.

What is regenerative medicine?

Regenerative medicine is an emerging, but fast-moving, field of healthcare with the potential to transform lives for the better. It covers a wide range of therapies designed to enable damaged, diseased or defective skin, bone and other tissues and even perhaps organs to work normally again. Regenerative medicine is a high value science-based manufacturing industry whose products will provide economic and social impact in treating the UKs ageing population.

[The] EPSRC Centre for Innovative Manufacturing in Regenerative Medicine is to become the go to place for manufacturing research for this emerging industry.
Taking Stock of Regenerative Medicine in the United Kingdom, BIS Office for Life Sciences, July 2011

The UK has the chance to be a leader in this eld [regenerative medicine] and this opportunity must not be missed the UK could and should be a world leader in this eld.
House of Lords Science and Technology Committee report on Regenerative Medicine, July 2013

We are pleased to be able to once again present the Annual Review of the EPSRC Centre for Innovative Manufacturing in Regenerative Medicine. While the rest of the Review focuses on the excitement of the science and detail of our impacts, the aim of this introduction is to set this in the international and national context. The last year has been a very significant year for the Centre including preparation for, and enacting the outcomes of, our international mid-stage review, understanding and accommodating changes in the national research environment, and the securing of additional funding to sustain some of the work of the Centre beyond the EPSRC initial funding. Perhaps the most significant event for the Centre operationally has been our international mid-stage review. The panel for this was chaired by Michael May, President and CEO of the Centre for Commercialization of Regenerative Medicine (CCRM), Toronto, and included international and national academic and industrial members in addition to EPSRC and TSB observers. We are pleased to be able to report that the mid-stage review had a positive outcome with recognition of the role and potential of the Centre nationally and internationally. The reviewers did, however, advise us that there were some things that we needed to consider and address in particular a need to think bigger and more strategically with respect to our project portfolio. There is more on the consequences of the review later in this document.

translational Hubs and for clinical applications. Further EPSRC support for the Centre has also been secured by Rob Thomas and Nick Medcalf in competitions for Early Career Fellowships and for Manufacturing Fellowships, respectively. The coming year will see an increased focus on securing Technology Strategy Board funding with industry partners and in establishing a way of working with EU partners for the Centre and other academic regenerative medicine manufacturing researchers. Our parallel research training activity, the EPSRC Doctoral Training Centre for Regenerative Medicine, has graduated its first cadre of PhDs over the past year and prepares for its final intake of students under the current funding model. Outreach has also moved up a gear during the year, we welcome Sophie Dale-Black into her full-time role as Outreach Manager. Outreach has included hosting the first EPSRC Manufacturing the Future Conference in September 2012, on behalf of the broader national academic community in manufacturing. We have also exposed early career regenerative medicine manufacturing academics from around the country to Boston-style academic innovation with the support of the Science and Innovation Office at the British Consulate-General. We have also started our programme of research sandpits, the first in Bath focused on making living bone, and lots of it. More on outreach and our plans for it can be found later in the report. We would like to thank our collaborators for their support over the year and our researchers for their efforts, and wish to particularly thank our international reviewers for their work on our behalf. We are also grateful to Leo Enright for his contribution to our outreach programme prior to Sophies arrival. Regenerative medicine as a field is now maturing as is demonstrated by the increasing engagement of Government in its support and the increasing interest of large pharmaceutical companies in its exploitation this means that manufacturing as one of the key steps to commercialisation can only become more important and that the depth and utility of science that we need to generate to operate in this highly regulated world will only increase. There is much for us to do together!

03 | annual review

Executive Summary 2012-2013

This Annual Report gives an overview of the mission and activities of the EPSRC Centre for Innovative Manufacturing in Regenerative Medicine following its third year of operation. The Centre is led from Loughborough University, in partnership with complementary groups at Keele University and The University of Nottingham.

Nationally, Government has confirmed that regenerative medicine is one of the eight great technologies which will propel the UK to future growth and the preliminary findings of the Witty Review of Universities and Growth show the strategic role of the Centre and its partners in this as does the Report of the House of Lords Science and Technology Committee on Regenerative Medicine. The Centre had the privilege of giving evidence, including oral evidence, to the latter. In parallel with this high level activity, the practical role of the Centre in the UK innovation system and its way of working has become clearer. The signing of a Memorandum of Understanding with the Cell Therapy Catapult in January was an important step and the Centre and the Catapult are now working together on projects with UK industry leaders. The recent results of the UK Regenerative Medicine Platform (UKRMP) competitions confirm that Centre partners are the collaborators of choice through their securing of funding as partners within both

David Williams and Richard Archer, August 2013

Core Theme:

04 | annual review

05 | annual review

Manufacturing and Automation

Access to regenerative medicine products could reverse the trend of treating many chronic and life-threatening diseases palliatively, or of simply delaying the progression of diseases. Therapies that can cure or significantly change the course of diseases will extend and improve quality of life, while reducing the financial burden on our healthcare system. As regenerative medicine products evolve, regulation is clarifying the requirements of platforms to deliver the medicines to the patient and systems for the manufacture and supply of the products. One of the foci of the EPSRC Centre addresses the challenges of the straightforward, consistent, cost effective supply of autologous (developed from the patients own tissues) cell therapies in hospital settings. These therapies target musculoskeletal disease, incontinence, cardiovascular disease and some forms of leukaemia. A micro-factory or clinic close to the bedside represents a significant clinical and business opportunity and would enable wide uptake of regenerative medicines.

Hydrogels for treatment of intervertebral disc degeneration

Chronic low back pain caused by intervertebral disc (IVD) degeneration can interfere with the ability of people to participate in regular daily activities. In this project, we have designed and formulated biodegradable synthetic polymer composite candidates with physico-chemical and mechanical properties representative of nucleus pulposus tissue, a jelly-like substance found in the middle of the spinal disc. We will select which of these candidate polymer composites, when photo-crosslinked, has the capability to promote and control the differentiation of human mesenchymal stem cells to the nucleus pulposus phenotype under physiologically relevant environmental conditions, including controlled O2 concentration and mechanical stress. We are developing a prototype bioreactor platform providing mechanical stimulation in a controlled hypoxia environment, simulating in vivo conditions for stem cell and nucleus pulposus tissue engineering applications. We are also developing a prototype device that will allow delivery of these injectable scaffolds during minimally invasive spinal surgery. Project team: Yang Liu, Deepak Kumar (Loughborough University), Nick Forsyth (Keele University) Collaborators: Fondazione Filarete, Ruskinn Technology, ElectroForce Systems Group Bose

Development and validation of an Instron TGT hydrostatic bioreactor for tissue processing in regenerative medicine
This project has shown that hydrostatic pressure applied to cells in culture leads to an increase in bone cell growth and mineralisation, two processes highly important for the regeneration of skeletal tissue. The novel Instron TGT bioreactor allows standard format cell culture plasticware to be used, with additional control over frequency and amplitude of hydrostatic pressure applied. Such a design will allow large scale-up for manufacturing of cell-based therapy applications. Results indicate that externally applied hydrostatic pressure delivered by the bioreactor can independently stimulate bone growth and also act synergistically with soluble factors added into the cell culture media to enhance bone development in the laboratory. This bioreactor design could therefore be applied to cell-seeded 3D scaffolds for laboratory conditioning prior to their implantation in patients. This project was referenced within the House of Lords Science and Technology Committee Report on Regenerative Medicine, published in July 2013. Project team: Alicia El Haj, James Henstock, Yvonne Reinwald (Keele University) Collaborators: Instron TGT, Nanofiber Solutions

Exploring the feasibility of a new regulatory paradigm for the manufacture of autologous cell therapies
Attempting to reach a widely spread patient population with an autologous cell therapy is extremely challenging as economies of scale-up do not apply and there is the potentially formidable cost of demonstrating comparability for additional manufacturing sites through clinical trials. A modified regulated manufacturing model more appropriately satisfying the comparability requirements of regulators to demonstrate equivalence for additional manufacturing sites would permit access to a wider patient population and allow the clinical need to be met with greater efficiency. This project addresses important issues identified by the TSBfunded VALUE project and the EPSRC Centres Near Patient Cell Processing project. Assessments will be undertaken of alternative regulated manufacturing models to identify the scientific barriers that must be overcome in order to permit the successful implementation of the preferred approaches. The project is shaped by an expert external reference team, allowing debate and steering while removing bias. Project team: David Williams, Paul Hourd, Amit Chandra, Patrick Ginty (Loughborough University) Advisors include: Athersys, GSK, Smith & Nephew, MHRA, independents

To view all our research projects, please visit bit.ly/RM_Research

Core Theme:

06 | annual review

07 | annual review

Characterisation and Control

The regenerative medicine industry requires the manufacture of high quality medical products at an economically acceptable cost. The safe and reproducible delivery of a viable regenerative medicine product is key to its success, and in-process characterisation of the cells, the scaffold and the combined product will lower costs by reducing operatorto-operator variability in culture processes, allowing objective characterisation and comparison of different cell lines and identifying baseline parameters for long term monitoring of cell lines. One of our approaches, quality by design (QbD), offers companies a great opportunity to achieve this. Quality by design uses risk management and manufacturing engineering tools to define critical parameters and operating tolerances to control product development and production quality. Quality by design will facilitate faster product approval and more efficient manufacture to tighter specifications. Quality by design requires an improvement in the capability of measurement tools to inform process development. The EPSRC Centre investigates the key research challenges of developing and applying quality by design enabling measurement tools.

Non-invasive, label-free quantitative characterisation of live cells in monolayer culture

Cellular feedstocks underpin many regenerative medicine therapies, and effective in-process monitoring for large-scale manufacture would be highly beneficial for ensuring high quality products are produced consistently at an economically acceptable price. This project has focused on the construction of a novel optical total internal reflection microscope, capable of imaging sub-micron particles and the cellular membrane, and acquiring sequential bright field and phase contrast images of different fields of view. This technology uses a label-free approach to deliver video monitoring of live cells in higher resolution than has previously been possible and will be applicable to quantitative in-process analysis, relating cell quality to treatment outcomes for stem cell therapies. Our live cell imaging technique has attracted the interest of researchers from Moorfields Eye Hospital, London, who are investigating corneal regeneration. The live cell imaging technique will be valuable in further understanding cell well-being and allowing optimised design of cell treatment strategies. Project team: Melissa Mather, Mike Somekh, John Crowe, Virginie Sottile, Jing Zhang, Ed Morris, Stephanie Strohbuecker, Rebecca Choi, Kelly Vere (The University of Nottingham) Collaborators: ReNeuron, Moorfields Eye Hospital

From science bench to clinical application: Establishing a stem cell population with consistent therapeutic behaviours
A major concern in the application of stems cells in the clinic is the structural and clinical variability in the outcome, which limits standardisation of stem cell-based therapies and hampers comparison of clinical study outcomes. The growing interest in human mesenchymal stem cell (hMSC) purification and culture for cell therapies highlights the need for mammal models to evaluate clinical efficacy and standardise procedures. This project aims to deliver tools required to achieve reproducible and consistent cell populations for future clinical studies. We follow well-characterised cells as they move along the translational pipeline, determining the quality parameters of hMSCs using biologically relevant models. We have shown that the antigen-induced arthritis model is a relevant preclinical model that allows input and output variables to be measured and assessed over a short time period. Oksana Kehoe is supported by a Fellowship from the Institute of Orthopaedics. Project team: Oksana Kehoe, Alicia El Haj, James Richardson (Keele University), Robert Thomas (Loughborough University) Collaborator: Institute of Orthopaedics

Using Quality by Design (QbD) approaches to reduce risk and optimise cell therapy manufacture
This project focuses on the application of quality by design (QbD) approaches to understand and reduce the risk of cell product failure as a result of poor manufacturing process control. This provides an exemplar of a methodology for process design space definition that is necessary to de-risk cell therapy manufacture for regenerative medicine. Applying QbD principles to the development of a design space and operating space for the cryopreservation of human stem cells, the project has established a robust method for measuring cell viability after a cryopreservation process. This method has proven suitable in defining the operating space for cell banking and product thawing. In applying statistical tools and QbD principles to cell product manufacturing, the method provides a route for industrial partners wishing to reduce risk and regulatory uncertainty. Project team: Robert Thomas, Elizabeth Ratcliffe, Paul Hourd, Peter Mitchell (Loughborough University) Collaborator: Neusentis

To view all our research projects, please visit bit.ly/RM_Research

Core Theme:

08 | annual review

09 | annual review

Delivery and 3D Products

Step-change improvements are needed in the methods by which cells, particularly stem cells, are stored, transported and delivered into the body. One of the major challenges remains in the provision of commercially viable manufacturing and logistics systems. The delivery of cells to the patient in a clinical setting raises scientific and technological challenges. Simple injection of cell suspensions into a disease site is inefficient, resulting in wastage of cells, compromised viability of the medicine and poor starting conditions for the regeneration of the target tissue. The EPSRC Centre investigates the development of materials to aid cell delivery to the target tissue, with a particular focus on the challenges of creating reproducible 3D scaffolds.

A new 3D delivery platform for regenerative medicine

The development of novel materials to aid scale-up of stem cell culture is of great commercial value and strategic importance to the regenerative medicine industry. Materials used for the manufacture of stem cells, as well as their in vivo transport, are important for cell survival, separation and processing. This project develops new materials that allow cell growth within supporting scaffolds and the separation of cells through the use of a magnetic field. The scaffolds have been designed so that cells can be captured within them during assembly of the material, and released safely through scaffold disassembly. Both 2D and 3D systems have been investigated for cell culture use, leading to an exciting proposition for large scale-up of cell-based products. The systems have been tested for cytocompatibility and repeated cell culture of a variety of cell types useful for regenerative medicine. Project team: Kevin Shakesheff, Cameron Alexander, Aram Saeed (The University of Nottingham), Alicia El Haj (Keele University), Robert Thomas (Loughborough University), Brian Saunders (The University of Manchester) Collaborator: RegenTec

Defining and manufacturing a cell therapy product for the generation of bone in spinal surgery applications
This project develops manufacturing methods for cell delivery systems aimed at unlocking the potential of autologous stem cell therapy in the regeneration of bone in the vertebrae. A major problem in the treatment of vertebral fractures is the mismatch in mechanical properties between bone and the implants used to provide an instant fix to the break. Over time this mismatch can result in complications due to further fractures and weakening of the surrounding bone. Our new approach is to define a product that allows the patients own bone marrow derived stem cells to be located around a porous implant. Over time these cells form new bone tissue and take over the mechanical function of the implant. The project combines polymer processing, microtechnology, rheology and stem cell biology. The project has resulted in the invention of a new injectable delivery system that integrates with existing stent technologies. This system will be developed with commercial partners in the future. Project team: Kevin Shakesheff, Lisa White, Felicity Rose (The University of Nottingham) Collaborator: Nottingham University Hospitals NHS Trust

Manufacturing delivery systems for neuronal grafts

This project enhances the international reach of the EPSRC Centre, working with Israel-based internationally-leading scientists focused on developing human embryonic stem cell therapies for Parkinsons disease. The work builds on our concept that the final cell product should include a delivery system, embedding an EPSRC Centre-designed manufacturing and delivery system into a new cell therapy. The research focuses on thre e critical issues: the risk of tumour formation post-transplantation, the poor survival and functionality of the graft and the manufacturing of the final product. Once validated in vitro, the new microparticle delivery system will be tested in vivo for lack of tumour formation, proper integration and for corrective/regenerative effects of the grafts. Completion of our tasks would enable progression into more advanced stages of cell therapy testing in primates and ultimately humans. This project has been co-funded by the British Israel Research and Academic Exchange Partnership Regenerative Medicine Initiative (BIRAX). Project team: Kevin Shakesheff, Felicity Rose (The University of Nottingham) Collaborator: Hadassah Hebrew University Hospital, Israel

To view all our research projects, please visit bit.ly/RM_Research

Our Latest Research Projects

As part of our preparation for, and follow-up to, the mid-stage review, we analysed the strengths and outcomes of our research and considered the direction of travel within the regenerative medicine industry. We have drawn together a number of challenge-led disruptive projects which will maintain our position at the cutting edge of regenerative medicine manufacturing research. These coordinated projects are due to begin in October 2013 and collaborative partners will be sought during the first phase of each project.

10 | annual review

11 | annual review

Bespoke near-patient delivery of bio-printed bone

The feasibility of delivering bio-printed bone to patients where bespoke products are created close to the patient will be investigated, and the clinical delivery process for this will be mapped. Understanding the limitations that this process places on the level of validation that can be conducted at the delivery site is a key outcome of this project.

Application of closed loop control to centralised manufacture of cell therapies

This project will investigate ways in which the logistical demand of end-point product testing can be reduced through the use of closed loop control at centralised manufacturing facilities. This will involve the application of new technologies to enable alternative modes of delivery to the patient.

Regulatory considerations for both centralised and near-patient manufacturing and delivery
The EPSRC Centre has unique measurement capabilities that can be mapped to the in-process or end-of-process requirements for product manufacture, and these will be further developed to reduce risk and optimise the logistics of manufacture and clinical release. Combining these measurement capabilities with regulatory science activities will develop a consensus on viable manufacture and delivery processes and their pathways through regulation.

The new projects address specific issues in the logistics of manufacturing and delivery of cell therapy products. A product must meet specific criteria in order to be accepted by regulators as being fit for purpose. Measurement at different points during the manufacturing process will provide assurance of quality, however confidence is needed in the particular measurement protocols. Measurement strategies will therefore significantly affect the practicalities and logistics of manufacturing and of the release of the product to the clinic and patients. A range of representative exemplar products are to be progressed within the EPSRC Centre that require different manufacturing, measurement and release strategies.

To view all our research projects, please visit bit.ly/RM_Research

12 | annual review

13 | annual review

Key Outputs from our Work

House of Lords Science and Technology Committee Report on Regenerative Medicine, July 2013
The report makes recommendations to the Government that, if acted upon, would facilitate the translation of scientific knowledge into clinical practice and encourage its commercial exploitation. For more details, please visit http://bit.ly/RM_Lords David Williams attended the initial roundtable workshop that sought to provide the Committee with an opportunity to discuss the Regenerative Medicine Inquiry with academic experts, industry representatives, funding organisations and representatives of the Department of Health, the Department for Business, Innovation and Skills and the Technology Strategy Board. David also provided oral evidence on regenerative medicine manufacturing to the Committee on behalf of the EPSRC Centre, alongside Keith Thompson of the Cell Therapy Catapult and David Newble of TAP Biosystems.

Application of response surface methodology to maximize the productivity of scalable automated human embryonic stem cell manufacture
E. Ratcliffe, P .C. Hourd, J. Guijarro-Leach, E. Rayment, D.J. Williams, R.J. Thomas, Regenerative Medicine, 2013, 8, 39-48 To read the paper, please visit http://bit.ly/RM_Paper1 The cost and quality of regenerative medicine manufacture is notoriously difficult to control due to highly complex processes with poorly defined tolerances. As a step to overcome this, this paper demonstrates the use of quality-by-design tools to define the operating space for economic passage of a scalable human embryonic stem cell production method with minimal cell loss.

Precision manufacturing for clinical-quality regenerative medicines

D.J. Williams, R.J. Thomas, P .C. Hourd, A. Chandra, E. Ratcliffe, Y. Liu, E.A. Rayment, J.R. Archer, Phil. Trans. R. Soc. A, 2012, 370, 3924-3949 To read the paper, please visit http://bit.ly/RM_Paper2 This paper demonstrates the precision automated manufacture of living materials, particularly the expansion of populations of human stem cells for therapeutic use as regenerative medicines. The paper also describes quality engineering techniques for precision process design and improvement, identifying the requirements for manufacturing technology and measurement systems evolution for such therapies.

Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro
J.R. Henstock, M. Rotherham, J.B. Rose, A.J. El Haj, Bone, 2013, 53, 468-477 To read the paper, please visit http://bit.ly/RM_Paper3 Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. This paper demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo.

A study of enzymatic activity in cell cultures via the analysis of volatile biomarkers
T.W.E. Chippendale, B. Hu, A.J. El Haj, D. Smith, Analyst, 2012, 137, 4677-4685 To read the paper, please visit http://bit.ly/RM_Paper4 Aldehyde dehydrogenase enzymes are responsible for the metabolism of aldehydes, including acetaldehyde, and are linked to disease. This paper describes a method to study aldehyde dehydrogenase activity in cell cultures involving the measurement of acetaldehyde concentrations in the gas/ vapour phase. The method uses selected ion flow tube mass spectrometry (SIFTMS), developed for the rapid quantification of trace gases in humid media, and the results of the study indicate that SIFT-MS gas phase analysis could be applied to the study of volatile metabolites of intracellular enzyme reactions - thus having potential utility in disease research and drug discovery.

Gelation of microsphere dispersions using a thermally-responsive graft polymer

N.N. Shahidan, C. Alexander, K.M. Shakesheff, B.R. Saunders, J. Colloid Interface Sci., 2013, 396, 187-196 To read the paper, please visit http://bit.ly/RM_Paper5 This paper investigates mixed microsphere/thermally responsive polymer dispersions that exist as particle gels at 37C. A thermally responsive polymer containing a cationic backbone and poly(2-(2-methoxyethoxy)ethyl methacrylate) side chains has been synthesised. Dispersions of this polymer with the poly(caprolactone) microspheres form weak gels at 20C, yet at higher temperatures they form stronger gels due to a combination of bridging of the microspheres by the polymer and reinforcement of the polymer network. The gels have the potential to be used as injectable scaffolds for tissue engineering applications. The EPSRC Centre has patent applications pending for scaffold manufacture from responsive magnetic particulate dispersions for ex-vivo cellular expansion, and the HypoxyCOOLTM process (see page 16).

Leveraged Projects: UK Regenerative Medicine Platform

The Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC) have established a 25million UK Regenerative Medicine Platform (UKRMP) to address the technical and scientific challenges associated with translating promising scientific discoveries in this area towards clinical impact. As part of the initial activities of the UKRMP, four interdisciplinary and complementary research Hubs have been established which together provide a world-leading programme to promote the development of regenerative therapies. EPSRC Centre academics are involved in three of the four Hubs, including directing one Hub. These three Hubs are described here.

14 | annual review

15 | annual review

Acellular (smart material) approaches for therapeutic delivery

Director: Kevin Shakesheff (The University of Nottingham) EPSRC Centre member within core team: Alicia El Haj (Keele University) This Hub will develop platform technologies that use materials and drugs to orchestrate cells to regenerate tissue. In regenerative medicine applications, the cells that generate new tissue can either reside within the patient or be administered as a therapy. In both cases there is a need to create an environment in vivo that facilitates tissue formation. Therapeutic delivery systems build on principles of biomaterials design and drug delivery to create final products in which the efficacy of cell therapies or the mobilisation of the patients own stem cells are maximized. The core team is composed of materials scientists and stem cell biologists from The University of Nottingham, Imperial College, The University of Manchester, Keele University and The University of Southampton. This team has experience in the design of advanced materials for medical applications.

Engineering and exploiting the stem cell niche

Director: Stuart Forbes (The University of Edinburgh) EPSRC Centre member within core team: Alicia El Haj (Keele University) The niche that surrounds stem/progenitor cells in developing or damaged organs has a profound effect upon the stem/progenitor cells. The focus of this Hub is to exploit therapeutically the communitys understanding of the biology of stem niches. The Hub will use this knowledge to optimise the growth and differentiation of stem cells and improve organ regeneration through endogenous repair and cell transplantation. The research team comprises academics from The University of Edinburgh, The University of Bristol, The University of Cambridge, Imperial College, Keele University, Kings College London, The University of Manchester and The University of Strathclyde. Alicias contribution to the Hub will be in the area of bioreactors and in vitro conditioning for tissue growth.

The pluripotent stem cell platform

Director: Peter Andrews (The University of Sheffield) EPSRC Centre members within core team: David Williams, Robert Thomas, Nick Medcalf (Loughborough University) Advances in human pluripotent stem cell biology provide unprecedented opportunities to generate safe donor cells for all human tissues and organs in virtually unlimited numbers. Harnessing these advances will enable an array of novel cellmediated therapies. Realising these ambitions requires a translational structure that melds fundamental discoveries into a pipeline for medical products and applications. The research team comprises academics from The University of Sheffield, Loughborough University, The University of Cambridge, The Wellcome Trust Sanger Institute, The Babraham Institute and NIBSC. Contributions to the Hub by David, Rob and Nick will include addressing challenging cell manufacturing and supply issues for clinical applications for both minimally manipulated and advanced therapeutic medicinal products.

To view all our research projects, please visit bit.ly/RM_related

Working with our Centre:

16 | annual review

17 | annual review

Case Studies of Successful Collaborations

Tackling the challenges of scale-up and manufacturing The Cell Therapy Catapult
The Cell Therapy Catapult has joined forces with EPSRC Centre members at Loughborough University to work together on innovative manufacturing. The two organisations will collaborate to develop robust processes and new manufacturing and delivery techniques, removing the barriers associated with turning cell-based therapies into products, and providing training and skills development. Tackling some of the challenges associated with scale-up and manufacturing of cell therapies such as ensuring reproducibility, purity, potency and efficacy is a key objective for the Cell Therapy Catapult.

Designing new manufacturing processes HypoxyCOOL

HypoxyCOOL began life as a collaborative project between the EPSRC Centre and Ruskinn Technology Ltd, one of the worlds leading suppliers and manufacturers of anaerobic and modified atmosphere workstations. Ruskinn was recently acquired by The Baker Company, USA. HypoxyCOOL is a patent-pending process that pre-conditions liquid media from an ambient (or unknown) oxygen concentration to a user-defined oxygen level, within a short period of time. It is a vital step for improving cell yield and reducing artefact-driven, gene expression changes in tissue culture processes. The process provides precisely pre-conditioned media to very low levels of dissolved O2, it maintains media sterility and it is fully compatible with tri-gas incubators or hypoxia workstations.

A pipeline of collaborative projects Blood pharming

As part of a DARPA-funded consortium led by Celgene Cellular Therapeutics and also including TAP Biosystems, EPSRC Centre members have researched novel cell culture technologies, process characterisation and optimisation to enable in vitro manufacture of red blood cells (erythrocytes) using progenitor cells from human umbilical cord blood. This project led to two additional complementary investments. The first is an EPSRC Early Career Fellowship for Robert Thomas, where he will determine the conditions required to economically grow different types of blood cells in large, clinically useful numbers, and also determine how tolerant the manufacturing process is for the repeated production of safe and effective cells. Rob will collaborate with TAP Biosystems and the Fred Hutchinson Cancer Research Centre, USA. The second investment utilises funding from the EPSRC Centre and the Wellcome Trust to collaborate with an existing Wellcome Trust-funded consortium seeking to produce red blood cells in the laboratory. The consortium comprises The University of Bristol, The University of Edinburgh, The University of Glasgow, NHS Blood and Transplant, the Scottish National Blood Transfusion Service, the Irish Blood Transfusion Service and Roslin Cells. The expanded consortium is currently seeking additional funding to translate this research from bench to bedside.

Automating the cell culture process The ambr

A practical infrastructure to enable large-scale, economically-viable manufacture of regenerative therapies must be established before these scientific discoveries can make a real difference to the world. EPSRC Centre members at Loughborough University are working with TAP Biosystems, a world leader in the design and development of innovative automation for life science applications, to ensure that its academic expertise is transferred through to the industrial landscape. One example of a collaborative project with TAP Biosystems is the demonstration of a range of applications of a new advanced micro bioreactor system, now commercially available as the ambr. The ambr uses cost-effective, disposable micro bioreactors controlled by an automated workstation, thus enabling significant savings on materials and labour.

We are delighted to be working with academic experts at Loughborough University on the techniques needed to turn smallscale cell therapies into robust products amenable to larger-scale manufacture. This is one of the fundamental translational gaps that the Cell Therapy Catapult is working to bridge, providing the cell therapy industry with important advances, and the expertise available will be invaluable for this task.
Keith Thompson, Chief Executive, Cell Therapy Catapult

The EPSRC project has provided the essential proof of principle for HypoxyCOOL, and through such support has better ensured positive outcomes both in terms of the application of autologous cell production and adding value to the Ruskinn business.
Huw David Thomas, UK Commercial/Sales Manager, Ruskinn Technology Ltd

Scientific and engineering advances made by Dr Rob Thomas group at the EPSRC Centre for Innovative Manufacturing in Regenerative Medicine were critical to a DARPA-funded stem cell-derived red blood cell program.
Dr Stewart Abbot, Executive Director Integrative Research, Celgene Cellular Therapeutics

Collaborating with commercially driven UK researchers is resulting in developing novel automation, which will secure future sustainable production of affordable cell therapies.
Dr David Newble, CEO, TAP Biosystems

18 | annual review

19 | annual review

Our Outreach Programme

Our academic outreach work has developed significantly since the 2011-12 review report, and here we summarise just a small number of the activities that have taken place or are ongoing.
Enhancing outreach within the UK: We have identified regional outreach contacts at key universities in the North, Mercia, South  East and South West regions of the UK please see the Boston mission article on page 20 for their profiles. Activities and events will be focused within these areas, in particular our sandpit events. P  artnering with other groups: In order to maximise the benefit to the community, we complement existing networks efforts by
partnering on activities. An example is the joint event organised by the EPSRC Centre and the London Regenerative Medicine Network (LRMN) in November 2012, which featured talks by international opinion leaders Peter Zandstra (Toronto) and Robert Deans (Athersys). In October 2013, we will co-host an event with the HealthTech and Medicines KTN on Getting the product to the patient.

New outreach project: Modular manufacture of bone constructs for large scale reconstruction
There is an unmet clinical need for large scale, live tissue augments to replace skeletal anatomy following tumour resection and to fill segmental defects resulting from trauma. Developing a modular approach to the manufacture of bespoke large scale augments represents a niche area within the market that has the potential to be rolled out to provide a range of solutions across the entire sector. This new project will unlock a toolbox of solutions for surgeons to improve the surgical outcome and thus quality of life for patients, reducing costs to the NHS and providing a lucrative commercial entry into the bone substitute market. The long term goal is large scale bone reconstruction using a combination of particles with different properties, housed in a titanium shell. The aim of this project is to fabricate a sub-unit of the full scale design to demonstrate the viability and function of the bone. Particles with different cell types and/or growth factors, modular constructs, can be combined in the desired proportions; here two modular constructs will be used one with osteoblast-like cells and another with endothelial cells. Project team: Marianne Ellis, Irene Turner (The University of Bath), Liam Grover (The University of Birmingham), Lucy Foley (Newcastle University), Bram Sengers (The University of Southampton), Peter Mitchell (Loughborough University).

Public engagement Biology Builders and schools outreach

Regenerative medicine and tissue engineering featured at the Royal Society Summer Science Exhibition for the first time in 2013. Led by Kevin Shakesheff, Glen Kirkham, Lisa White and Adam Taylor (The University of Nottingham) and supported by members of the EPSRC Centre and the EPSRC DTC, the Biology Builders demonstrations were shown at the six-day Summer Science Exhibition. The Exhibition is an annual display of the most exciting cutting-edge science and technology in the UK, and this year 12,500 visitors attended. Focusing on learning outcomes of the complexity of the organs in our body and that scientists aim to build new organs in the future, the Biology Builders demonstrated optical tweezers and 3D printing techniques to members of the public and school groups of sixth form students. The Biology Builders were interviewed by BBC World Service and for the Guardians Science Weekly podcast. The Biology Builders team are grateful for funding from the ERC, the EPSRC and The University of Nottingham.

Skills and people development focus: Our industry is rapidly developing, and a highly skilled workforce will create an efficient,  productive and motivated industry. We will focus on skills development through activities aimed at giving researchers a higher level of business acumen and increasing their employability in the industry, and we will highlight alternative careers to researchers and graduating PhD students seeking non-academic experience.

Community-engagement events Themed sandpits

A key mechanism within the EPSRC Centres outreach programme is an event we call a sandpit. A sandpit is an event with a specific theme where people from a variety of disciplines come together to respond to the theme by creating novel projects. Activities at sandpits allow people to brainstorm ideas, create teams and develop project proposals. These projects are then pitched to a decision-making panel, who will decide which to fund based on the quality and novelty. It is intended that the winning projects at sandpits will have clear pathways to applying for additional funding from another source, for example Research Councils UK or EU funding. Direction of the sandpits by clinicians and/or industry is key to their success. The first outreach sandpit, hosted by The University of Bath in our South West region, had the theme Manufacturing-enabled orthopaedic interventions using regenerative medicine approaches. One project was selected by the panel to receive 40,000 funding, and this project is described opposite. Our second outreach sandpit will be hosted in October 2013 by Newcastle University in our North region and will have the theme Pancreatic islet processing for clinical transplantation: from mysterious art to reproducible science. Future sandpits will be hosted by The University of Birmingham in our Mercia region and University College London in our South East region.

Introducing our National Centre Outreach Manager Sophie Dale-Black

Sophie Dale-Black joins us from The University of Nottingham. Sophie studied medicinal and pharmaceutical chemistry and holds a PhD in X-ray crystallography. She has skills in the facilitation of interdisciplinary research collaborations, the bespoke design of collaboration-building events and in business development, operations management and project management. Sophie has already been on the road meeting some of the community, and she would be pleased to hear from anyone interested in the research and activities of the EPSRC Centre.

E-TERM Fellows Samantha Wilson and Qasim Rafiq have recently undertaken outreach to schools by delivering workshops to AS and A2 sixth form students at Brine Leas High School, Nantwich. The Fellows covered material relevant to the National Curriculum, as well as engaging in topical discussions surrounding the use of stem cells and highlighting the potential impact of the research.

20 | annual review

21 | annual review

Our Outreach Programme

International Outreach
The EPSRC Centre recently undertook a mission to Boston, USA, in collaboration with the Science and Innovation Network at the British Consulate-General, to explore the biomanufacturing activities ongoing in Massachusetts and to develop new relationships for cooperation in cell therapy and regenerative medicine. The mission delegates had the opportunity to meet with many Boston organisations, including the MIT BioMAN Research Program site, the Harvard Stem Cell Institute, the Massachusetts Life Sciences Center and companies Xcellerex and Joule Unlimited. Importantly, the mission allowed the promotion of the UK communitys capabilities to a highly relevant US audience, sowing the initial seeds for future international collaborations.

Regulatory Science
...the science that will inform and enable robust regulatory decisions by both influencing and informing the regulator and assisting the manufacturer in providing the knowledge base to deliver confidence in these products.
EPSRC Centre Manufacturing Industrial Summit, 2012

Promoting the UKs academic capability

Proles of mission delegates:

Marianne Ellis
The University of Bath
South West Outreach Contact

Since our 2012 summit we have refined our work in regulatory science by seeking consensus on the research questions to be addressed and methods used. We have begun a major new EPSRC Centre project identifying preferred alternative approaches for autologous cell therapy manufacturing, a key enabler for the rapid take-up of clinician-led therapies. The work of our new EPSRC Manufacturing Fellow, Nick Medcalf, has a strong regulatory science component. We have also begun to work with EPSRC and MHRA to define other areas for work by the research community.

In performing outreach work as a National Centre, the EPSRC Centre has the opportunity to promote the UKs capability in regenerative medicine manufacturing. We will host a catalogue of equipment and facility resources held across the academic community, enabling the identification of opportunities for equipment access and exchange, enhancing collaboration, and the identification of gaps in the national infrastructure portfolio. Utilising a bespoke instance of Kit-Catalogue, a system designed by Loughborough University, we will incorporate our equipment and facility catalogue into a wider database of academic institutions active in the area of regenerative medicine manufacturing, thus further enabling collaboration between institutions. It is hoped that promoting academic capabilities will also lead to new collaborations between academic, clinical and commercial organisations.

Lucy Foley
National Biologics Manufacturing Centre
North Outreach Contact

Liam Grover
The University of Birmingham
Mercia Outreach Contact

Ivan Wall
University College London
South East Outreach Contact

Marianne is a Senior Lecturer in Biochemical Engineering. Her research addresses the challenges of scale-up that are currently being faced in cell therapies, using bioreactor and bioprocess design, applied to cell expansion and growing tissue engineered cell-scaffold constructs for regenerative medicine.

Lucy was formerly a Lecturer in Biopharmaceutical Process Development at Newcastle University and has recently joined the National Biologics Manufacturing Centre as Lead Biopharmaceutical Engineer. Her interests lie in the achievement of robust supply models for cell therapies including production process industrialisation, supply chain development and live cell shipment. She is a founding member of the ATMP Manufacturing Community (AMC).

Liam is a Professor in Biomaterials Science and his research focuses on characterising the interactions between biological systems and materials. Liams research aims to regenerate not only bone, but structures that lie on the interface between hard and soft tissues. Liam was promoted to Professor in early 2013.

Ivan is a Lecturer in Regenerative Medicine Bioprocessing. His research interests focus on strategies to improve retention of cells for direct delivery and tissue engineering. He is also developing methods for measuring cell function and potency to improve therapeutic outcomes. Rob Thomas, David Williams and Leo Enright accompanied the delegates and we are grateful to Sarah Hokanson of the Science and Innovation Network for her support.

We are engaging with key social science academics at the ESRC Innogen Centre, The University of Edinburgh, and at The University of York. In 2014, we will hold an intensive workshop on regulatory science issues with contributions from stakeholders having clinical, industry, regulatory and standards perspectives. Participants will also debate how approaches to regulation can influence macro-economic performance. The workshop, and our participation in other international initiatives, will identify key areas of regulatory science for manufacturing where Centre leadership will complement the initiatives of other global leaders.

we recommend that the TSB and EPSRC undertake an annual stock-take of regenerative medicine manufacturing capacity and make recommendations to BIS about future needs
House of Lords Science and Technology Committee report on Regenerative Medicine, July 2013

building stronger links between the regulators and those who are regulated would be a vital step in overcoming the difficulties of GMP requirements.
David Williams quotation from House of Lords Science and Technology Committee report on Regenerative Medicine, July 2013

People Development:

22 | annual review

23 | annual review

Doctoral Training and E-TERM Fellowships

Stuart Jenkins Keele University The EPSRC Doctoral Training Centre (DTC) in Regenerative Medicine is a parallel collaboration between Loughborough, Keele and Nottingham. Its aim is to provide research training in regenerative medicine across the whole of the translational research continuum for research students coming from an engineering and physical science background. This year has seen the first graduations by DTC students, who have obtained postdoctoral roles including positions at the Anthony Nolan Cell Therapy Centre, Queensland University of Technology (Australia), National University of Ireland - Galway, Loughborough University, The University of Nottingham and Keele University. In collaboration with the EPSRC DTC at Leeds, Sheffield and York, funding was secured from the EPSRC for the Engineering, Tissue Engineering and Regenerative Medicine Landscape Fellowship Programme. The E-TERM Programme funds ten 2-year, early career fellowships, and to date four fellowships have started, with a further two being awarded during the summer of 2013.
Fellowship theme: Magnetic nanoparticle-mediated delivery of therapeutic genes Developing safe, effective tools to genetically engineer cells prior to cell transplantation could produce a step-change in the treatment of debilitating CNS injury and disease. Stuarts fellowship seeks to enhance the efficiency of magnetic nanoparticle-mediated therapeutic gene delivery to neural cells by applying a novel oscillating magnetic array (magnefect-nano). Stuart is working closely with nanoTherics, a Keele University spinout company. Stuart has degrees in both computer science and biochemistry/ neuroscience, with a PhD in biomedical engineering.

Qasim Rafiq Loughborough University

Fellowship theme: Microcarrier-based human mesenchymal stem cell culture There is significant interest in utilising human mesenchymal stem cells (hMSCs) for cell-based therapies. With potential lot sizes of billions (if not trillions) of cells required however, it is clear that a large-scale supply of fully characterised hMSCs is required. By combining a high-throughput approach with key analytical techniques (metabolomics, proteomics and metallomics), Qasims fellowship will focus on making informed advancements in the bioprocess development of microcarrier-based hMSC culture. This will result in an optimised, scalable and standardised manufacturing platform for clinically-relevant hMSCs. Qasim has an MEng in biochemical engineering and achieved a PhD in regenerative medicine through the EPSRC DTC.

lida Ortega The University of Sheffield

Fellowship theme: Development of tissue-engineered stem cell niches for corneal repair Corneal disease is the fourth largest cause of blindness worldwide and one of the many causes of the loss of corneal transparency is total limbal stem cell deficiency. Limbal stem cells are crucial for tissue regeneration and the ability of these unique cells to self-renew is thought to be partially due to their location within protective niches with intricate physical, metabolic and biological characteristics. lidas fellowship aims to design and manufacture models of the limbus in which to study limbal stem cell behaviour. lida is collaborating with The Electrospinning Company Ltd, EBERS and Keele University.

Samantha Wilson The University of Nottingham

Fellowship theme: Development of a novel human corneal substitute There is a clinical need for the development of a reliable artificial and healthy biomimetic cornea. Samanthas fellowship will take corneal eye-bank tissue deemed unsuitable for transplantation, develop decellularisation techniques and replace the cells with new cell populations derived from stromal and epithelial cells. This will contribute healthy, reliable corneas for drug and toxicity testing, and will also increase the availability of corneas for transplantation. Samantha has a degree in biological and medicinal chemistry and biology, and achieved a PhD in regenerative medicine through the EPSRC DTC. Samantha is also a qualified teacher.

To view profiles for our DTC students, please visit http://bit.ly/RM_DTC

lida has a degree in chemistry and a PhD in bioengineering.

Katie Glen
Loughborough University
24 | annual review 25 | annual review

People Development:

Researcher Proles
Under the guidance of project leaders at Loughborough, Nottingham and Keele universities (see pages 28 and 29), a highly skilled team of researchers undertake cutting edge research projects within the EPSRC Centre. Here we celebrate the researchers diverse skills and backgrounds, and acknowledge their considerable contribution to our work and the wider field of regenerative medicine manufacturing.

Katie Glen is a Postdoctoral Research Associate at Loughborough University. She studied for a medical science degree and has a PhD in cardiovascular sciences. Prior to joining Loughborough University, she worked for Protagonist Therapeutics, Inc. as part of the biology R&D team. She is a multidisciplinary scientist with a research focus on innovative manufacturing and biological engineering for healthcare technologies.

Paul Hourd
Loughborough University Paul Hourd is the EPSRC Centres Programme Manager, based at Loughborough University. Paul has a degree and a PhD in biochemistry. He has worked for much of his career in user-led product and process design and development within the in vitro diagnostics and cell-based therapeutic areas. His industrial experience includes six sigma black belt expertise applied to the improvement and validation of GMP-compliant manufacturing processes. Paul previously worked as Project Manager for the EPSRC-funded remedi Grand Challenge project at Loughborough University and his research focuses on regulatory science and quality engineering approaches to bioprocessing and translation of cell based therapies for regenerative medicine.

Oksana Kehoe
Keele University Oksana Kehoe is a Research Fellow at Keele University and the Acting Head of the Rheumatology Research Laboratory at Robert Jones and Agnes Hunt Orthopaedic Hospital. Oksana has a degree and a masters in immunology and a PhD in biochemistry. Her research focuses on inflammatory diseases, in particular rheumatoid arthritis, where she investigates mesenchymal stem cells as therapeutic agents. Oksana has research experience from positions at Taras Shevchenko National University of Kyiv (Ukraine), Cardiff and Manchester universities.

Forhad Ahmed
Loughborough University Forhad Ahmed is a Postdoctoral Research Associate at Loughborough University. Forhad has a degree in applied biology, a masters in immunology and a PhD in haematology. His research focuses on the production of cultured red blood cells from adult and embryonic stem cells in a scalable suspension format.

Amit Chandra
Loughborough University Amit Chandra is a Postdoctoral Research Associate at Loughborough University and he has both a degree and a PhD in chemical engineering. Amit is the engineering technical lead for the set-up and validation of the Cell Therapy Manufacturing Facility at Loughborough University. He has experience in working in hospital settings and previously worked on the EPSRC-funded remedi Grand Challenge project.

Deepak Kumar
Loughborough University Deepak Kumar is a Postdoctoral Research Associate at Loughborough University. He has a degree in biomedical materials science and engineering, a masters in cell and tissue engineering and a PhD in biomedical engineering. Deepaks research addresses the development of novel photo-curable polymer hydrogels for the encapsulation of human mesenchymal stem cells and their differentiation towards a nucleus pulposus like cell type by mimicking the in vivo hypoxic and mechanical stimulation environments.

Thomas Chippendale
Keele University Thomas Chippendale is a Postdoctoral Research Associate at Keele University. He holds an MEng degree in biochemical engineering, and gained a PhD in regenerative medicine through the EPSRC DTC. Thomas research is focused on the potential of a real time trace gas analytical technique (selected ion flow tube mass spectrometry) for non-invasively monitoring the progression of cell cultures.

Alex Lyness
Loughborough University Alex Lyness is a Postdoctoral Research Associate at Loughborough University. Alex has a degree in product design and manufacturing engineering, a masters in engineering design and a PhD in healthcare engineering. His research focuses on the investigation of drug delivery systems, and he is exploring methods to deliver conventional pharmaceuticals and emerging biopharmaceuticals, importantly including cell-based therapies.

Yvonne Reinwald
Keele University Yvonne Reinwald is a Postdoctoral Research Associate at Keele University. She has a masters in medical biotechnology and a PhD in tissue engineering. Yvonnes research focuses on the evaluation of the performance of bioreactors for tissue engineering and clinical application by investigating the growth environment (changes in physiological parameters and physical forces) that cells and cell-constructs are exposed to during mechanical stimulation.
26 | annual review 27 | annual review

People Development:

Researcher Proles
Mark McCall
Loughborough University Mark McCall is a final year PhD Student at Loughborough University and will become a Postdoctoral Research Associate by October 2013. Mark has a degree in physics with medical physics, and is completing his PhD in cell therapy manufacturing, studied through the EPSRC DTC. His research addresses the prediction and reduction of cell therapy cost of goods and regenerative medicine manufacturing technology. Mark has secured a Loughborough University Enterprise Fellowship to further develop a novel manufacturing system designed during his PhD.

Aram Saeed
The University of Nottingham Aram Saeed was a Postdoctoral Research Fellow at The University of Nottingham until July 2013. He has both a degree and PhD in pharmacy. Arams research addresses the development of 3D smart substrates for the expansion and manufacturing of stem cells. Aram is now a Lecturer within the School of Pharmacy at The University of East Anglia, and he continues to collaborate with the EPSRC Centre.

Jing Yang
The University of Nottingham Jing Yang holds a Nottingham Research Fellowship and he has a PhD in biocomposites. Jings research focuses on the fabrication of human tissues using 3D printing. In particular, he is researching the printing of hepatocytes and other cells in the liver to mimic natural tissue-tissue interfaces and reproducing liver functions. These tissues can potentially be used for drug screening and toxicology.

Peter Mitchell
Loughborough University Peter Mitchell is a Postdoctoral Research Associate at Loughborough University. Peter has a masters in biology from The University of Bath and a PhD in skeletal tissue engineering from The University of Southampton. His research focuses on tissue engineering and the development of cell-based therapies. He is currently working on applying quality by design concepts to process design and optimisation in the manufacture of cellular therapies.

Lisa White
The University of Nottingham Lisa White is a Postdoctoral Research Fellow at The University of Nottingham. She holds a degree and a PhD in chemical engineering. Lisas research focuses on bone regeneration, in particular in using different platforms of materials, cells and growth factors. Lisa has considerable experience in outreach and seeks out opportunities to communicate her research to the public.

Andrew Picken
Loughborough University Andrew Picken is a Postdoctoral Research Associate at Loughborough University. He has a degree in microbiology and a PhD in biotechnology. Andy is a cell biologist interested in bioprocessing, and has previously worked at The University of Manchester and UCB-Celltech. His current research addresses the improvement of cryopreservation in order to provide safer preservation of cells needed for regenerative medicine applications.

Ian Wimpenny
Keele University Ian Wimpenny is a Postdoctoral Research Associate at Keele University. He holds a degree in medical materials science and a PhD in biomedical engineering. His research is at the interface between biology and materials and focuses on real-time methods for characterising both the degradation of materials and how this affects the growth and activity of cells. Ian will be moving to a Postdoctoral Research Associate role at The University of Manchester in September 2013.

Elizabeth Ratcliffe
Loughborough University Elizabeth Ratcliffe is a Postdoctoral Research Associate at Loughborough University. She holds a degree in microbiology, a masters in molecular medical microbiology and a PhD in molecular microbiology and vaccine research. Elizabeth has worked with leading national and international commercial and academic collaborators to establish manufacturing processes and application of quality process engineering principles (6 , QbD) for human stem cell-based products.

Jing Zhang
The University of Nottingham Jing Zhang is a Postdoctoral Research Fellow at The University of Nottingham. She has a masters in optical engineering and a PhD in electrical and electronics engineering. Jings research focuses on the design and development of advanced microscopy for biological research and on surface plasmon resonance microscopy for sensing biomolecular interactions and for imaging living cells.

28 | annual review

29 | annual review

Leadership Team
Richard Archer - Chair
Richard Archer is an engineer and robotics specialist who was a founder of both The Technology Partnership in Cambridge and subsequently The Automation Partnership, where he was CEO until retiring in 2004. He was the founding chair of the RegenMed Industry Group at BIA and continues to consult for international corporations on business strategy in regenerative medicine and stem cells.

Key People

Cameron Alexander

School of Pharmacy The University of Nottingham

Eleri Bristow

School of Mechanical and Manufacturing Engineering Loughborough University

Lee Buttery

School of Pharmacy The University of Nottingham

Karen Coopman

Chemical Engineering Department Loughborough University

John Crowe

Division of Electrical Systems and Optics The University of Nottingham

David Williams - Director

David Williams has held senior leadership positions in academia and industry, working for much of his career at their interface. Focused on healthcare and pharmaceuticals over the past fifteen years, David has previously worked with the automotive, aerospace, food and electronics sectors. He has been Professor of Healthcare Engineering in the Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University since 2003.

Sophie Dale-Black

School of Mechanical and Manufacturing Engineering Loughborough University

Chris Denning

School of Medicine The University of Nottingham

Nick Forsyth

Institute for Science and Technology in Medicine Keele University

Sourav Ghosh

School of Mechanical and Manufacturing Engineering Loughborough University

Chris Hewitt

Chemical Engineering Department Loughborough University

Alicia El Haj - Co-Director

Alicia El Haj is Chair of Cell Engineering and Director of the Institute of Science & Technology in Medicine at Keele University. She has been involved in bringing together interdisciplinary groups within biomedicine, physical sciences and engineering interested in aspects of cell and tissue engineering. She holds a Royal Society Wolfson Research Merit Award and is Chairman of the European Council of the International Society for Tissue Engineering and Regenerative Medicine (TERMIS).

Paul Hourd

School of Mechanical and Manufacturing Engineering Loughborough University

Yang Liu

School of Mechanical and Manufacturing Engineering Loughborough University

Melissa Mather

Division of Electrical Systems and Optics The University of Nottingham

Nick Medcalf

School of Mechanical and Manufacturing Engineering Loughborough University

Jon Petzing

School of Mechanical and Manufacturing Engineering Loughborough University

Kevin Shakesheff - Co-Director

Kevin Shakesheff is Chair in Tissue Engineering at The University of Nottingham and he is the founder of RegenTec, co-founder of Critical Pharmaceuticals and co-founder of the UK Tissue and Cell Engineering Society. Kevin qualified as a pharmacist in 1992, and his research focuses on the integration of cell biology and tissue engineering. Kevin holds a Royal Society Wolfson Research Merit Award.

Svetan Ratchev

Division of Manufacturing The University of Nottingham

James Richardson
Institute for Science and Technology in Medicine Keele University

Paul Roach

Robert Thomas - Deputy Director

Robert Thomas is a Senior Lecturer at Loughborough University and an EPSRC Early Career Fellowship holder. He has worked with leading regenerative medicine companies to establish manufacturing processes for cell based products. The focus of Robs research is the innovation and exploitation of healthcare technologies and regulated manufacturing for the commercialisation of regenerative medicine products.

Institute for Science and Technology in Medicine Keele University

Felicity Rose

School of Pharmacy The University of Nottingham

Joel Segal

Division of Manufacturing The University of Nottingham

Michael Somekh

Division of Electrical Systems and Optics The University of Nottingham

Virginie Sottile

School of Medicine The University of Nottingham

To view profiles for academic team, please visit http://bit.ly/RM_academics

The EPSRC Centre Collaborator Network

Association of British Healthcare Industries Anthony Nolan Trust Arthritis Research UK Athersys Inc. BIA Cell Therapy and RM Industry Group British Standards Institution Capsant Neurotechnologies Celgene Cellular Therapeutics Cell Medica Cellon CELLutions Biosystems Cell Data Services Cell Therapy Catapult Ceram CM Technologies Cook MyoSite Critical Pharmaceuticals Cytori Therapeutics Dana-Farber Cancer Institute Electroforce Systems Group, Bose Corporation Epistem Fondazione Filarete Fraunhofer IGB Fujifilm Diosynth Biotechnologies Future Health Technologies GE Healthcare Life Sciences GlaxoSmithKline Hadassah Hebrew University Hospital, Israel Haemostatix Harvard Stem Cell Institute HealthTech and Medicines KTN Institute of Orthopaedics Instron TGT Intercytex Keranetics Kitenics Lonza McGowan Institute of Regenerative Medicine MedCell Medicines and Healthcare Products Regulatory Agency Medilink EM Medilink WM Mel Chemicals MICA Biosystems Moorfields Eye Hospital NHS Foundation Trust Morgan Technical Ceramics Nanofiber Solutions National Institute for Biological Standards and Control National Physical Laboratory NC3Rs Neusentis Newcastle Upon Tyne Hospitals NHS Foundation Trust NHS Blood and Transplant NHS East Midlands Strategic Health Authority NHS Technology Adoption Centre Nottingham University Hospitals NHS Trust Organogenesis Pfizer Precision Cleanrooms RegenTec Reinnervate ReNeuron RepRegen Roslin Cells Ruskinn Technology SCA Cool Logistics Sigma Aldrich Smith & Nephew TAP Biosystems TiGenix UCL Gene Therapy Unit UK Stem Cell Bank Unilever University Hospitals of Leicester NHS Trust VetCell Videregen Wake Forest Institute for Regenerative Medicine WiCell Research Institute

Centre for Innovative Manufacturing in Regenerative Medicine

Research enquiries: Prof David Williams EPSRC Centre Director Professor of Healthcare Engineering Loughborough University Leicestershire LE11 3TU T +44 (0)1509 227668 E d.j.williams@lboro.ac.uk Outreach and general enquiries: Dr Sophie Dale-Black National Centre Outreach Manager Loughborough University Leicestershire LE11 3TU T +44 (0)1509 227649 E s.h.dale-black@lboro.ac.uk

@RM_Outreach

www.epsrc-regen-med.org