Research projects

Inflammation and Repair - Regenerative Medicine - IVD regeneration - current projects (projects)

Efficacy testing of stem cell based tissue engineering therapies for intervertebral disc regeneration using a novel ex vivo model of human intervertebral disc degeneration

Abstract

Low back pain (LBP) is the leading cause of disability in the UK, affecting 1.1 million people and costing over £12 billion per annum. In the majority of cases LBP is associated with intervertebral disc (IVD) degeneration. Current surgical treatments focus on pain relief, and often involve invasive surgical interventions (e.g. spinal fusion), which have poor outcomes.

We have extensively investigated novel adult mesenchymal stem cell (MSC)-based tissue engineering therapies for regeneration of the degenerate IVD and are collaborating with biomaterials experts to develop and optimise novel, injectable hydrogels which mimic the gelatinous core of the IVD, the nucleus pulposus (NP). Notably we have already demonstrated that MSCs are capable of differentiation to NP-like cells in such hydrogels and now wish to translate this through to clinical intervention. However, current animal models do not accurately mimic the human IVD or disease pathophysiology and thus for clinical translation a more appropriate model system for efficacy testing is required. We have designed a novel bioreactor which can mimic the load and humoral (low glucose, pH, oxygen and osmolarity) environments of the normal and degenerate human IVD and have validated an in vitro loaded whole-disc explant model within this system. The proposed PhD studentship will advance this work through the application and testing of our novel biomaterials and cell-based tissue engineering strategies within this unique ex-vivo system. 

 

The aims are to:

  1. Induce degeneration in normal IVD tissue from bovine caudal IVD (obtained from a local abattoir) by surgically injuring them and subjecting them to physical/biochemical factors present within the IVD within our bioreactor. This will act as a model of early human IVD degeneration (which cannot be studied in animals) and will allow the student to:
    • assess novel biomaterial hydrogels with regards to their suitability for minimally invasive implantation (i.e. injection), and biomechanical properties;
    • assess the differentiation of human MSCs within biomaterial hydrogels under conditions which mimic those found within the human IVD
  2. Use degenerate human IVD tissue (from cadavers donated for research) to investigate whether MSCs injected within optimised biomaterial hydrogels differentiate and recapitulate normal NP matrix in the degenerate “niche”.

 


 

Duration of the project

October 2011 - September 2015

Funding bodies

  • Research Council Doctoral Training Grant (MRC, BBSRC, EPSRC)
  • Faculty of Medical and Human Sciences

Members of the project

Professor Judith HoylandPrincipal investigator
Dr Stephen RichardsonPrincipal investigator
Louise ClarkePhD student