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For more information, go to www.arthritisresearchuk.org

A new era for osteoarthritis treatment

Published on 01 November 2011
Source: Arthritis Today

Rubbing hands

Arthritis Research UK launches its fourth national centre of excellence this month. The team behind the new tissue engineering centre predict that within five years, using keyhole surgery they will be able to treat people with osteoarthritis with adult stem cells to regenerate damaged joints, delaying the need for joint replacement. And that’s just for starters. Arthritis Today reports on an exciting new initiative.

 
Arthritis Research UK is launching a major experimental tissue engineering initiative which seeks to regenerate bone and cartilage by transplanting stem cells into the damaged joint.

The exploratory research has the potential to revolutionise the treatment of osteoarthritis, which causes pain and disability to 10 million people in the UK. Patients currently undergo joint replacement surgery but only when the disease has deteriorated to severe end stage. Treatment options for early osteoarthritis are usually limited to non-surgical options such as painkillers and physiotherapy.

The £6million Arthritis Research UK Tissue Engineering Centre is led by Newcastle University and is based at four sites across the UK: Newcastle University, the University of Aberdeen, Keele University/the Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust/Keele University and the University of York.

Within five years, researchers at the centre aim to treat osteoarthritis by introducing stem cells into damaged joints via keyhole surgery.

They hope that in future years they may be able to perform this as a ‘one-stop’ day case arthroscopic procedure, delaying or reducing the need for joint replacement surgery. Other long-term aims include finding a way to ‘switch-on’ stem cells already present in patients’ joints which might involve creating new biomaterials. Researchers also hope to develop injectable preparations and an ‘off the peg’ bank of universal donor cells for use in any patient, making treatment cheaper and more widely available.

Professor Alan Silman, medical director of Arthritis Research UK, said: “This early experimental work is the first step on a journey that could one day end the need for joint replacement operations.

“It’s hugely exciting. At the moment joint replacement surgery is the most effective treatment we have but we have to allow people with osteoarthritis to deteriorate until they reach a suitable point for surgery. This means patients are living for years with increasing pain and disability which impacts their quality of life.”

Professor Andrew McCaskie, centre director and professor of orthopaedic surgery at Newcastle University’s Institute of Cellular Medicine, said: “Every patient has their own ‘repair kit’; whereas joint replacement surgery replaces the damaged tissue with engineered metal and plastic, we’re trying to assist the human body to repair itself.

“Keyhole and minimally invasive operations for early arthritis have been in development for some years and we propose to improve upon these techniques and work towards more widely available treatments. This requires research at all levels of the process, from laboratory to bedside. We’re confident that elements of this approach will reach the patient in the operating theatre within the first five years.”

Professor Silman continued: “Osteoarthritis of the hip and knee will be an increasing problem in our society as people age and want to remain active. Although joint replacement can be spectacularly successful, finding an injectable cell-based answer that could be used earlier would be a major breakthrough, reducing pain and disability and minimising health service costs. We believe our new centre will lead the way in this exciting field of research.”

The Arthritis Research UK Tissue Engineering Centre is funded by a core grant of £2.5 million over five years from Arthritis Research UK with a further £3.4 million pledged by the four participating universities. The centre will bring together leading clinicians, engineers and biologists from research and clinical groups.

"Every patient has their own ‘repair kit’; whereas joint replacement surgery replaces the damaged tissue with engineered metal and plastic, we’re trying to assist the human body to repair itself." - Professor Andrew McCaskie

What each centre will do?

 
Professor Cosimo Dr Bari

Principal investigators in Aberdeen, Professors Cosimo De Bari, Richard Aspden, James Hutchison and David Reid will focus on:

 

• Developing and validating tests or assays, which will identify markers in patients’ stem cells before transplantation surgery, allowing doctors to predict and measure the potency of the cells being used. It is hoped that this will enable doctors to predict in advance of surgery which patients will do well, and which stem cells are the most effective. This work will be done in conjunction with Keele/Oswestry.

• The stem cells that are naturally present in the joints, called endogenous stem cells. This will help to devise novel ways in which to intervene in the process of osteoarthritis by manipulating and influencing the behaviour of these stem cells. They plan to do this by administering drugs that target the endogenous stem cells in the joints or by introducing a special 3D matrix to the area of damaged cartilage, loaded with a growth factor or chemical that could attract the endogenous cells, to regenerate and even prevent the breakdown of cartilage and other tissues in osteoarthritis.

Dr Paul Genever

The York team, led by Dr Paul Genever, a senior lecturer in the department of biology, will focus on:


• The basic biology behind stem cells and how they function. The team will work with stem cells from the bone marrow of patients from local hospitals who have undergone hip replacement surgery.

• The specialist environment in which the stem cells live in the bone marrow, called the niche: a 3D structure of different cell types and components of a special matrix. The team will attempt to recreate the niche in the laboratory by combining stem cells with different cell types and matrix components. It is hoped that if the matrix is transplanted into damaged cartilage loaded with special chemicals or growth factors, it will regenerate cartilage and other tissues. 

Professor Andrew McCaske 

 

Newcastle, Professors Andrew McCaskie, Kenny Dalgarno, Anne Dickinson and Dr Mark Birch will focus on:

 

• Assessment of the immunogenicity of the stem cells from the same and a different donor and their interaction with new biomaterials for regenerative use.

• Enable the technologies to be translational to the clinic by the use of Good Manufacturing Practices (GMP) in their dedicated facilities.

• Investigating the manufacture of 3D matrices to support bone and cartilage regeneration, using special biomaterials which will slowly dissolve in the body as the natural tissue grows. The team will engineer new scaffold materials that fulfil the mechanical demands of tissue replacement surgery and also devise approaches to deliver chemical or growth factor cues that can control the rebuilding of bone and cartilage.

• Working towards clinical translation and surgical therapies. 

Professor Sally Roberts 

 

The Keele University and Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust led by Professors Sally Roberts, James Richardson and Alicia El Haj will focus on:

 

• Introducing modified process of cell therapy to the orthopaedic clinic. Professor of orthopaedic surgery, James Richardson, established special facilities for culture-expansion of autologous chondrocytes and marrow-derived mesenchymal stem cells for cartilage and bone repair over a decade ago. With Professor Sally Roberts, director of spinal research, they have been instrumental in monitoring progress in the clinic, developing outcome measures for objective assessment of the procedures used and studying the biology of repair. Professor Alicia El Haj examines ways of controlling, scaling-up production and targeting of cells for tissue-engineered cell therapy.

• With existing Arthritis Research UK funding, the team is about to trial the use of stem cells from bone marrow versus cartilage cells to treat osteoarthritis of the knee in a small clinical trial of approximately 100 people. (This trial, reported widely in the national media and in issue 149 of Arthritis Today, has been delayed, because of changes in the regulations governing the use of stem cells in trials. It is expected to start shortly).

• They will try and identify ‘risk factors’ or biomarkers to predict the small proportion of patients who do not respond so well to cell therapy.

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