School outreach programme

At the Institute for Science and Technology in Medicine (ISTM) we are committed to communicating science to the wider public and learners of all ages. Our students and staff have taken part in various public outreach initiatives and they are now writing for the Healthcare Engineering and Regenerative Therapies (HEART) blog. The HEART group is composed of researchers from Keele University, Loughborough University and Nottingham University.

James Henstock talking to pupils from Al Aqsa School

For the first time this year, we welcomed pupils from the Al-Aqsa School in Leicester who came to visit our research facilities. The school visit was organised as part of the HEART Outreach group’s school workshop programme and the Al-Aqsa School’s work experience week.

The group of year 9 and 10 pupils spent a day in ISTM’s laboratories at the Guy Hilton Research Centre and had the opportunity to participate in a range of activities related to the innovative work that is carried out at ISTM. These activities were led by post-graduate students, post-doctoral researchers and academics who demonstrated equipment and laboratory techniques with the aim of sharing our knowledge about stem cells; biomaterials; regenerative medicine; bioreactor technology; nanotechnology; magnetics; and cancer research.

Katie Bardsley giving a demonstration during the visit to the ISTM labs

With our school outreach programme and our passion for medical research we are hoping to communicate our work to new learners and the wider community, as well as to inspire more students to take up study in Science, Technology, Engineering and Mathematics (STEM) subjects. 

Healthcare Engineering and Regenerative Therapies (HEART) blog

Accelerating bone formation for the treatment of defects and fractures

Rapid, effective repair of large bone defects or fractures is still a challenging issue in orthopaedic surgery. If the defect or fracture is too large, natural bone repair often cannot occur and therefore, medical treatment is required. Cell therapy using either stem cells or bone cells is a promising new therapy for such cases. Clinical trials, however, have so far generated mixed results in terms of speed and quality of repair. Thus, improving bone formation is one of the hurdles in the translation of regenerative medicine for bone repair.

Bone has a unique ability to repair itself with the process of bone repair following the same pathway as healthy bone development. Direct or ‘intramembranous’ bone development within the body is characterised by a complex series of reactions which ultimately result in the growth of bone.

Inspired by natural bone formation, the Biomaterials Group at the Institute for Science & Technology in Medicine (ISTM), together with orthopaedic surgeon, Mr Konduru of the University Hospital of North Midlands (UHNM), have developed a simple and convenient technique to improve bone growth. This technique uses surface modification to change the environment the cells are grown in to force them to form clusters or aggregates of particular sizes. An osteoblast cell line and human bone marrow-derived stem cells have both been used to test this new bone growth method and have provided clear evidence that the aggregates produced from this technique can enhance bone formation by following the same pathway as natural bone growth or repair (Figure 1). 

Figure 1: SEM elemental analysis showing calcium production in bone aggregates and monolayer samples after 3 day osteogenic stimulation. A: big aggregate; B: small aggregate; C: monolayer 

Cell aggregation is an essential step in natural ‘intramembranous’ bone formation because the way in which the cells are in contact with one another induces several events to take place to form an osteoid which will then become the centre for new bone formation. Our data has shown that growing osteoblast cells in aggregate form can generate far more mineralised matrix (the building blocks of bone) than culturing them in a standard monolayer fashion. Furthermore, the size of the aggregate has a significant influence on the mineral content and composition within that bone aggregate. Four important molecules required for the formation of bone, COL1, ALP, OPN and OCN, displayed different expression patterns depending on the aggregate size (Figure 2).

Figure 2: Prediction and matching of the gene expression of different osteoblast culture environments (monolayer, small and big aggregate) in the bone development stages.

It is therefore proposed that growing bone cells in an aggregate form will encourage them towards developing bone, while the size of the aggregate will determine how quickly they will develop bone. This aggregation study offers a simple but effective model that can be used to quickly create high quality bone for use in fundamental investigations or even clinical applications.

Focusing ‘big science’ on the microscopic detail of Alzheimer’s disease

Physicists, chemists and material scientists have developed an army of high-tech tools to probe the chemical and magnetic properties of materials at length scales of about 1/10000th of the width of a human hair (i.e. the nanoscale). In particular, x-ray techniques have evolved that can study such materials in minute detail and in non-destructive ways.

Chemical map of an aggregate of the Alzheimer’s disease peptide amyloid-beta (blue), and accumulated iron (red), obtained using the synchrotron x-ray technique known as spectromicroscoppy

Our research in this area is concerned with applying some of these techniques, previously exclusive to the realms of physics and chemistry, to the study of biological materials. These experiments require the use of synchrotrons such as the Diamond Light source in Oxfordshire, which are giant donut-shaped x-ray machines that can generate intense beams of x-ray light 10 billion times brighter than the sun. Other important requirements of synchrotrons are the ability to focus the light into microscopic probes, and the production of light with a full spectrum of wavelengths (just like the light from the sun).

Combining these properties enables us to perform both microscopy (creating nanoscale images of our samples) and spectroscopy (measuring a property of our sample as the x-ray wavelength is scanned). In fact, the latest state-of-the-art instruments enable us to combine these techniques into a process known as spectromicroscopy. Here we obtain a set of nanoscale images at many different x-ray wavelengths. This enables us to measure the distribution of the chemical and magnetic properties of our sample across regions as small as a few nanometers. It is therefore possible to study how different materials interact at the length scales of relevance to biology.

In our work we are interested in how a specific biological peptide known as amyloid-beta, which is implicated in the pathology of Alzheimer’s and other diseases, interacts with different forms of iron that occur naturally in our bodies. Using spectromicroscopy we were have been able to obtain chemical maps (such as the one shown below) that reveal the accumulation of iron (shown as red) within aggregates of the peptide (shown as blue) when incubated together in the laboratory. Combined with x-ray spectroscopy we were also able to show that the iron was slowly converted from a non-toxic form known as ferric iron, to a potentially neurotoxic ferrous form, following prolonged interaction with the peptide.

Alzheimer's disease is a major condition effecting increasingly large numbers of people, both old and young. The importance of this work is that it demonstrates a potential mechanism for the damage that occurs in the brain during Alzheimer’s disease. Using the same x-ray techniques we have now begun to study specimens of human brain tissue donated by Alzheimer’s patients, and can see interesting parallels in the nature of iron in these tissue samples compared to those we obtain in the lab. Understanding the role of iron in diseases such as Alzheimer’s is important for both early diagnosis using MRI scans, and for potential new treatments that could use the accumulated iron as a chemical target for drugs to attack.

FIRM Symposium 2014: Future investigators of regenerative medicine

FIRM (Future Investigators of Regenerative Medicine) is an early career network established in 2013 by four members (Hareklea Markides, Alex Lomas, David Smith and James Rose) of the EPSRC Doctoral Training Centre (DTC) in Regenerative Medicine based between Loughborough, Keele and Nottingham Universities. As young researchers, we recognise the importance of forming collaborative networks and so decided to bring together young researchers from across the world to form these networks early on in our careers. With this we give you the FIRM early careers symposium.

As early career researchers ourselves, we had a good understanding of what participants hope to gain from attending conferences and therefore tailored this conference to achieve just that. Held at the stunning Cap Riog Hotel in Girona, Spain, FIRM was designed in such a way as to encourage young researchers to get to know each other in a friendly and informal atmosphere, giving them an opportunity to present their work to an international audience. The symposium program was set up with plenty of time during the afternoons for socialising and networking.

After a successful 2013 symposium, we decided to hold the 2nd FIRM Symposium, FIRM 2014. For the second year running, we focused on the “Life Cycle of Cell Therapy”, capturing the topics of Fundamental Biology, Biomaterials, Enabling Technology, Clinical Translation, and Commercialisation. This focus allowed us to demonstrate how these fundamental topics are all interconnected and equally important in translating cell therapies from the laboratory to the clinic. Building on the participant feedback we received from FIRM 2013, we decided to incorporate additional interactive workshops focusing on: imaging modalities, commercialisation and communication skills. In conjunction with the communication skills workshop, we also recorded every students’ oral presentation to provide each speaker with a tool for reflection and improvement.

FIRM 2014 hosted eight world renowned international keynote speakers supported by 28 student oral presentations and 20 poster presentations. We are delighted to confirm that FIRM has now begun to build up a large network of early career researchers over the last two yeas, with collaborative work still ongoing from last years’ symposium, and new projects on the horizon.

We were amazed to see that over the last two years FIRM has attracted over 200 young researchers from over 60 research institutions across more than 20 countries. This has only been possible by the support from our mentors, our sponsors and of course our delegates.

The FIRM 2014 committee would like to thank all of the participants for creating such a vibrant and interactive atmosphere throughout the entire symposium. Without the sponsor’s generosity this symposium would not have been possible, so thank you! very much.

Translating technology from the laboratory to the clinic: Breath analysis and SIFT-MS

Medical applications of breath analysis go back more than 2000 years to Hippocrates, who noted the link between breath aroma and disease. However, it was not until the end of the last century and beginning of this century that developments such as gas chromatography mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry (PTR-MS) have helped to identify hundreds of volatile compounds in exhaled breath. More recently, the translation of technology from the laboratory into the clinic has led to the analysis of breath from patients with malignant and non–malignant diseases. While GC-MS and PTR-MS are largely qualitative techniques, SIFT-MS (developed at Keele University by Professor David Smith FRS and Professor Patrik Španěl) is both qualitative and quantitative. This allows the concentrations of specific breath markers, mostly volatile organic compounds (VOCs), in exhaled breath to be determined with accuracy and precision, and acceptable in clinical diagnosis. Breath sampling is non-invasive and can be achieved in real time with no discomfort to patients, including young children and frail patients. Hence, SIFT-MS has the potential to be a robust and valuable tool in support of clinical practice for disease diagnosis.

Management of lung cancer is an area where SIFT-MS has real potential. In the UK, just under 40,000 people are diagnosed with lung cancer each year. More important, it is the UK’s most common cause of cancer death for both men (24% of all cancer deaths) and women (20% of all cancer deaths). As early stage diagnosis is associated with increased survival rates, it is hypothesised that the detection of VOCs released by lung cancer cells would improve early diagnosis and prognosis. At present, assessment of a tumour’s response to treatment still relies heavily on imaging techniques such as chest X-Rays and CT scans. There is, therefore, great potential for a cheaper, on-line, radiation-free and non-invasive system that is capable of detecting and managing diseases, such as lung cancer. This is something that breath analysis and SIFT-MS may be able to offer in the near future.

Non invasive breath analysis—
Dr JosepSulé-Suso (right) with PhD student Abigail Rutter (left).   

Although much work has been carried out in the search for volatile biomarkers in exhaled breath of individuals with lung tumours, no single VOC or combination of VOCs have convincingly been identified. Over the last few years, we have carried out work at the Institute for Science & Technology in Medicine (ISTM) on the release of VOCs by lung cells in vitro. This research has shown that lung cancer cells have a VOC emission profile that seems to differ from their normal lung cell counterparts. These encouraging results are leading further work to unambiguously identify individual biomarker VOCs that could support lung cancer diagnosis. This should lead to the development and production of analytical instrumentation for real time breath analysis that could be readily utilised in hospitals and GP surgeries.

ISTM & hospital partners training Nigerian engineers: A boost for biomedical engineering in Africa

Biomedical Engineering (BME) is by its very nature a multidisciplinary occupation. It reaches from basic research into human physiology, through the development of devices and novel treatments for disease, to the translation and sustainable use of medical devices in the healthcare arena. An important area of BME is clinical engineering and the management of medical devices. Technology plays an increasingly important role in the delivery of healthcare services, and the proper management of medical technology is essential for ensuring the safe and efficient use of medical devices.

Left to Right: Kabiru Abdullahi; Dave Butler; Abdullahi Mu'azu Gigane; Garba Mohammed Ladan; Ed Chadwick; Aminu Sani; and Translate’s very own, Joseph Clarke.

The BME programme at Keele enjoys close links with the University Hospitals of North Midlands (UHNM), a relationship that has been built over the last 15 years that the course has been running. In recent years, the course has seen a growing interest in BME from students from a number of African countries including Uganda, Ghana and Nigeria. Many African hospitals now have substantial inventories of medical equipment, allowing them to deliver advanced patient care, and are realising the importance of properly managing that equipment to ensure the long-term viability of their clinical services.

Last year, a high-level delegation from Usman Danfodiyo University Teaching Hospital, in Sokoto, Nigeria visited Keele. They came to see the facilities we have to offer at the Institute for Science & Technology in Medicine (ISTM) and the Medical School, as well as the close links with UHNM and the support provided by the Clinical Technology Department led by Mr David Butler. This visit was initiated by a former student of our BME Masters programme, Mr Umar Mohammed, who impressed his managers with his ability to implement the skills he had learned here at Keele on his return to Sokoto.

A memorandum of understanding was subsequently signed between the Nigerian Hospital and Keele University to provide a customised, three-month training programme in Biomedical Engineering through ISTM, the School of Medicine and the Department of Clinical Technology at UHNM.

The first cohort of visiting engineers from Sokoto in Nigeria completed their training in Biomedical Engineering in December 2014. The trainees followed modules in Physiological Measurement and Medical Equipment Management, and spent four weeks on clinical placement at UHNM with a short training visit at our other hospital partner, the Robert Jones and Agnes Hunt Orthopaedic Hospital (RJAH) in Oswestry. The first four trainees to complete the programme, Aminu Sani Sokoto, Garba Ladan, Abdullahi Mu'azu Gigane and Kabiru Abdullahi, are shown below receiving their certificates with Dr Ed Chadwick, Program Lead, Mr Joseph Clark, Programme Administrator and Mr Dave Butler, Head of Clinical Technology at UHNM.

Building on this solid start to our relationship with Usman Danfodiyo, the hospital has sent another student to study for the MSc this year, and is currently discussing options for PhD studies and staff exchange. Keele is proud to be playing a role in the development of BME services by supporting educational provision in Nigeria.

Medical students visit from Saudi Arabia

For the fourth year, a group of students from the College of Medicine at Al Imam Muhammad Ibn Saud University in Saudi Arabia visited the Institute for Science & Technology in Medicine (ISTM) during August 2014.

Mr Mark Smith, Dr Paul Roach, Professor Andy Garner & other representatives from Keele University welcome the Saudi students.

The fourteen students and their tutor learnt about the latest research carried out at ISTM and the University Hospital of North Midlands (UHNM), including plenty of hands-on experience learning techniques and how to use the latest scientific equipment. Lectures included a visit to the Keele Active Virtual Environment (KAVE) and Anatomy Suite, and tours of UHNM departments such as the Cancer Centre and Obs & Gynae which host significant research projects involving UHNM patients. The students were also able to experience British culture with a traditional fish and chip dinner at the home of Mark Smith, ISTM's Research Manager.

The academic programme has been developed and managed by Dr Paul Roach, and this year the students were accompanied by Dr Waleed Al-Shaqha, Vice Dean for Research at Al Imam University. Dr Al-Shaqha took the opportunity to meet Professor Andy Garner, Dean of Health, and other key staff in the University and UHNM to discuss future collaborations, undergraduate medical student placements and research degrees.