| EPSRC Reference: |
EP/J501761/1 |
| Title: |
Cell labelling for in vivo use and in process quality control |
| Principal Investigator: |
Myers, Professor SR |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Blizard Institute of Cell and Molecular |
| Organisation: |
Queen Mary University of London |
| Scheme: |
Technology Programme |
| Starts: |
22 August 2012 |
Ends: |
21 August 2015 |
Value (£): |
163,600
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| EPSRC Research Topic Classifications: |
| Materials Synthesis & Growth |
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| EPSRC Industrial Sector Classifications: |
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Summary on Grant Application Form |
The clinical component of the project is a single clinical trial of the efficacy of spray cultured allogeneic keratinocytes in acceleration of re-epithelialisation of life-threatening burn injury [and other non-burn large area skin loss] split-thickness
skin graft donor sites based on a novel cell labelling system.
Whilst cultured keratinocyte allogeneic cells do not survive transplantation longterm, they appear to have a useful clinical role in both acute and chronic wound healing. In the former, they accelerate epithelialisation of partial-thickness cutaneous
wounds, and in the latter, they appear to convert the wound phenotype to a more acute one. These effects are mediated by the release of a wide range of cytokines and growth factors in an orchestrated way. The process of allograft cell loss is not
classical, has been described as creeping substitution and is poorly understood. The wound distribution of sprayed cells, their attachment and survival, and their subsequent migration have been almost impossible to follow in the absence of an in
vivo label [we have used sex-mismatching and a Y-probe in the past]. The effects can be seen clinically, but in a very subjective way as shortened "time to healing". A cell label will allow an assessment of the relative contribution of allogeneic
and autologous keratinocytes to accelerated restoration of epidermal barrier function over time.
This clinical study will establish the efficacy of spray cultured allogeneic keratinoyte adjuvant therapy at a new level of objectivity, and at the same time introduce a novel cell labelling system to the clinical environment. The population of lifethreatening
burn injury [>30% TBSA] has been chosen for a variety of reasons. This is the population for whom cultured keratinocyte stem cell technology has historically applied, since timely wound closure limits sepsis related mortality. Large
donor sites are created, and the patients return to theatre regularly, often daily, for further surgery or large dressing changes. This will allow longitudinal retrieval of punch biopsy material following spray application.
Three arms will be included, each represented by a 1% TBSA donor site wound:
- control donor site wound, managed in a standard way with Jelonet dressings,
- spray cultured allogeneic keratinocyte treated donor site wound,
- spray cultured allogeneic keratinocyte including cell label treated wound.
The wounds will be followed by serial clinical evaluation and standardised photography at dressing changes. 6mm punch biopsies will be retrieved from each site at T0, immediately following creation of the donor site, and two further time points
over the following two weeks - T48hrs and T5days ideally, but for ethical reasons at times otherwise when general anaesthetic procedures are required. Biopsies will be bisected and snap frozen or fixed for evaluation.
All patients will be adult, and recruited only with informed consent. A power calculation will be performed on statistical dvice, and a patient number of between 6 and 10 is currently anticipated. The work will be conducted by a Surgical research fellow toward a higher degree, MDRes or PhD under PI supervision.
The aspiration is for a detection system that will demonstrate the distribution, survival and migration of labelled allogeneic cells macroscopically. Tissue will be processed for detection of the cell label, for morphological evidence of foreign body
reaction or other, for the relative contribution of allo- vs autograft to volume, and for markers of keratinocyte migration, proliferation, differentiation and apoptosis.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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