Award details

Protection of tissue engineered cartilage by inflammation regulated transgenes

Reference	BB/C503954/1
Principal Investigator / Supervisor	Dr Michael Barker
Co-Investigators / Co-Supervisors	Dr Aileen Crawford, Professor Paul Hatton
Institution	University of Sheffield
Department	Genomic Medicine
Funding type	Research
Value (£)	125,575
Status	Completed
Type	Research Grant
Start date	01/01/2005
End date	31/03/2007
Duration	27 months

Abstract

We are developing tissue-engineered cartilage to repair arthritic or injured joints. One of the potential problems with this technique is that the engineered cartilage will often be introduced into an inflammatory environment which could damage the new tissue. We have recently shown that it is possible to use ex vivo gene therapy techniques to introduce protective genes into chondrocytes prior to engineering the cartilage, affording protection from the inflammatory environment. However if such genes maintain high levels of expression once the tissue is fully recovered, it could lead to abnormal cartilage growth. The aim of this project is to identify and incorporate promoters that are highly activated in an inflammatory environment but which are suppressed in a non-inflammatory one, enabling the therapeutic gene to be expressed only when needed. A range of potential promoters will be transiently introduced into well differentiated human chondrocyte cell lines, upstream of a luciferase reporter. Expression of the reporter will be determined in the presence or absence or various inflammatory cytokines. Promoters showing low endogenous activity but with high induction in the presence of inflammatory cytokines will be further screened in primary human chondrocytes. Successful candidate promoters will then be stably incorporated into primary chondrocytes upstream of the protective gene (tissue inhibitors of matrix metalloproteinase) and the cells expanded and used to construct tissue engineered cartilage. The ability of this transgenic tissue to survive cytokine driven inflammatory assault will be determined in an in vitro assay.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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