Cell labelling for in vivo use and in-process quality control

The future use of cells as both therapies and drug discovery tools addresses a huge unmet societal and clinical need
relating to a range of medical conditions, many with no current effective treatment option and representing a huge
disease burden. Over the last 10 years the exciting possibility of creating new therapies using living human cells has
matured to the extent that a small number of therapies exist and an emerging industry can clearly be identified. Cryoskin
is such a product, which is an active treatment for burns and hard to heal wounds (such as leg ulcers). This product
offering uses donor cells grown on selective materials specifically designed to promote cell growth, but then allow release
to the applied site of treatment. The product is being developed in a "spray" format to allow ease of clinical application.
However, it is necessary to be able to track and locate where the cells have been sprayed and to do this using reagents
that are non-toxic, remain within the cells for multiple generations and can be detected simply using a hand-held light
source following or during application.

This proposal is directly aligned to the development of a commercially viable product, with the labelling of Altrika's
Cryoskin product with a GMP synthesised/formulated cellular labelling reagent
which is known to be taken up by cells in a highly efficient fashion. These will then be evaluated by the team from The
Royal London Hospital to ensure that the labelling does not affect cell function and that patient care is improved. This
approach will allowing the delivery of stem cells into the clinical setting with direct tracking of the stem cell derived product
to the point of use.

This proposal brings together a synergistic team of chemists in Edinburgh (who have a long history of cell delivery
expertise) with direct day-to-day interaction with Altrika Limited who are world leading experts in cell based skin wound
care, Roslin Cellab who will assess the nature of the label on stem cell function and clinicians (The Royal London Hospital
and the Trauma Clinical Academic Unit of Barts) who will be using the labelled Cryoskin product.

Commercial: The UK PLC will benefit by strengthening the unique offering of Altrika, while solving a practical medical
need and allowing a "real" regenerative medicine product to become truly universally accepted and practical. Patients will
benefit by the availability of the "spray-cell" product that will help many seriously ill patients, often those with severe
burns.will allow all successful commercialisation routes to be explored in a responsive and dynamic manner.

Economic impact: This research programme will deliver vital underpining chemistry research to enable the delivery of the
broader biochemical goals in timely manner in a national and international setting. Both applicants have a history of
patent protecting appropriate discoveries and capitalising on discoveries. We will explore all avenues for the benefit of
the UK's economic competitiveness. The academic community will benefit from the tools developed in this programme
and importantly the chemistry developed will be applicable across the life sciences.

Broader Academic Impact: This research has significant academic (and commercial) potential impact. The ability to track
implanted stem cells is highly desirable from many academic and commercial angles and to have demonstrated this with
a cellular labelling agent clinically would open uyp a variety of doors. The research fellow employed in this project will
benefit in many ways, gaining many new cross-disciplinary skills, working between chemistry, biology and the clinic while
also working on translational skills.

General: An important generic skill is the ability to communicate and disseminate information: A multidisciplinary project
such as this will provide many opportunities for the involvement in public engagement and dissemination. Research
fellows of the group regularly participate in the School of College of Science and Engineering initiative "SciFun" and at the
Edinburgh International Science Festival. The 'Researchers-in-Residence' Programme places postgraduate students in
local secondary schools for short periods to interact on projects with 14 - 16 year old pupils. Dr DeSousa is committed to
high quality scientific communication and has taken part in a number of outreach activities promoting science and stem
cell research (e.g UK and Scottish Stem Cell Network Public Forums). There has been a significant amount of interest
surrounding Bradley's work resulting in frequent communication with the media. In February 2010 their work (DNA
Analysis by Dynamic Chemistry, Angew Chemie, 2010) was carried by Reuters and featured in more than 100 media
articles in countries across the globe such as ABC and the BBC. In January 2011 his work on polymers for platelet
activation was a full spread in the Sunday Scotsman (major Scottish newspaper), while his recent Nature Chemistry
paper (2011) was carried by all major TV and radio stations in the UK, Spain and Malaysia (where his collaborators came from).