Award details

Use of Mesenchymal Stem Cells for Enhancing Osseointegration of Implants.

Reference	BB/D014190/1
Principal Investigator / Supervisor	Professor Melanie Coathup
Co-Investigators / Co-Supervisors	Professor Gordon Blunn, Professor Jia Hua
Institution	University College London
Department	Institute of Orthopaedics
Funding type	Research
Value (£)	301,348
Status	Completed
Type	Research Grant
Start date	01/08/2006
End date	31/10/2009
Duration	39 months

Abstract

Mesenchymal stem cells (MSC's) are cells derived from the bone marrow which have great therapeutic potential in bone tissue engineering. MSC's are multipotent cells that can differentiate into many different cell types including osteoblasts, chondrocytes and adipocytes. By isolating these cells and expanding them in vitro, then re-introducing them at a later stage in vivo, it has been shown to aid bone healing where MSC's naturally play a role. A previous award winning study performed in the Centre (Mario Boni Award, European Orthopaedic Research Society, 2005) utilised the osteogenic potential of autologous bone marrow derived mesenchymal stem cells in an ovine bone tumour tibial mid-shaft model and results showed significantly increased bone formation and contact to the surface of the shaft of the implants in MSC treated animals when compared with untreated controls. This study sprayed MSC's in a fibrin glue matrix onto the implant surface. Autologous cultured bone-marrow derived mesenchymal stem cells were loaded within a fibrin glue carrier and sprayed under pressure onto a hydroxyapatite coated surface. This application using MSC technology has significant implications for the fixation of orthopaedic implants where enhanced bone regeneration is required and is a technique that can be applied to a number of orthopaedic implants used to treat degenerative bony conditions. For example in the UK there are over 9,000 revison hip operations performed annually and these patients would benefit from being able to regenerate bone adjacent to the implant. In this proposal, we aim to further investigate and optimse our spraying technique by asking the following questions: 1) Are allogenic MSC's as efficient as autologous MSC's? 2) Do differentiated osteoblasts lead to improved bone formation? 3)What is the optimal number of MSC's required for a maximum bony response? 4) What is the fate of these MSC's in vivo? To our knowledge we are the only centre using thisapproach to augment osseointegration and bone regeneration around implants. In this application we use fibrin glue as a carrier/scaffold and rely on the immediate strength of the implant. This is important as many applications of bone tissue engineering are initally inherently weak. Additionally most orthopadic applications involving metallic implants also require a joint replacement and in these situations a concept applicable to joint replacement arthroplasty is required. No published work to date has investigated the effect of cell number on bone formation. Although previous studies have indicated a role for MSC's in bone regeneration, its exact role in this process is unclear. Very few groups have attempted to label their implanted cells to track their direct contribution to bone growth. It is possible that instead of differentiating into osteoblasts directly that these cells may promote a suitable environment for bone healing and growth through their immuno-suppressive characteristics and anti-inflammatory effects. We therefore additionally ask the question of the benefit of implanting differentiated osteoblasts in the augmentation of bone formation and will track the implanted cells and monitor their migration. In our Centre we have been successful in differentiating MSC's along the osteoblastic, chondrocytic and adipocytic lineages and also in genetically labelling MSC's with the permanent label LacZ. These techniques would be utilised in this proposal.

Summary

When orthopaedic implants fail they do so by a reduction of bone stock adjacent to the implant surface and loosening of the fixation to the bony skeleton. The goal of this project is to use mesenchymal stem cells to regenerate bone adjacent to these implants and to improve implant integration with the skeleton. Mesenchymal stem cells (MSC's) are cells derived from the bone marrow which have great therapeutic potential in bone tissue engineering. MSC's are multipotent cells that can differentiate into many different cell types. By isolating these cells and expanding them in vitro, then re-introducing them at a later stage, it is possible to aid bone healing where MSC's naturally play a role. A previous award winning study performed in our Centre (Mario Boni Award,European Orthopaedic Research Society, 2005) showed significantly increased bone formation and contact to the surface of implants when treated with mesenchymal stem cells compared with untreated controls. This may have significant implications in reducing the failure rate of implants. This innovative study sprayed MSC's in a fibrin glue matrix onto the implant surface. In this proposal, we aim to investigate and optimse this technique by asking the following questions: 1) Are allogenic MSC's as efficient as autologous MSC's? 2) Do differentiated osteoblasts lead to improved bone formation? 3) What is the optimal number of MSC's required for a maximum bony response? 4) What is the fate of these MSC's in vivo?

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	Ageing, Industrial Biotechnology, Regenerative Biology, Stem Cells
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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