Monday 24 April 2017

Dr Danny Kelly Tissue engineering therapy to repair joint disease

dr danny kelly

A large proportion of patients presenting to orthopaedic surgeons with joint pain are suffering from osteoarthritis (OA), a disease of the joint, associated with significant degeneration of the articular cartilage that lines the surface of our bones.

The articular cartilage, a smooth tissue that covers the ends of bones where they come together to form joints, facilitates movement by allowing bones to glide over each other with very little friction.

Unfortunately, the tissue has a poor capacity for repair and therefore even small injuries or defects to the joint surface can progress to the painful and debilitating condition of osteoarthritis.

At present, the treatment options for OA are limited to surgical replacement of the diseased joint, such as a knee or hip, with a metal and polymer prosthesis. While this procedure is well established, it is not without its limitations and failures are not uncommon.

Joint replacement prostheses also have a finite lifespan, making them unsuitable for the growing population of younger and more active patients requiring treatment for OA.

The increasing prevalence of patients requiring treatment for OA is due to multiple factors, including lifestyle and occupational factors leading to increased incidence of trauma and greater levels of obesity in the general population.

Getting a joint replacement prosthesis at a younger age is a problem because you are more likely to outlive the prosthesis.

The field of tissue engineering has already led to the development of new treatment options to repair many different tissues and organs, including skin, blood vessels, trachea, bladder and bone.

These breakthroughs provide confidence that tissue engineering therapies will also one day provide a cure for OA.

In the future, it may be possible to tissue-engineer biological joint replacements prosthesis using stem cells, called mesenchymal stems cells (MSCs), that can be isolated within damaged or diseased joints to regenerate and repair articular cartilage which would prevent arthritis.

If successful, such a concept could form the basis of a novel tissue engineering therapy for treating degenerative joint disease such as OA.

Current cell-based therapies can be used to treat isolated cartilage defects which otherwise might lead to ostheoarthritis in the long-term, but at present cannot be used to treat the disease. Even their use as a treatment option for isolated cartilage defects is limited in a number of ways.

Firstly, the repair is often temporary, and secondly, widespread adaptation into the clinical setting is impeded by practical issues such as the high cost and time required for such procedures.

We are working on a project aimed at developing novel solutions to these problems.

Our work might provide a way to prevent ostheoarthritis occurring, by treating isolated defects that, left untreated, could lead to the development of the condition.

Firstly, we want to determine whether adult MSCs, freshly isolated from the injured joint, can be used to engineer functional cartilage tissue.

The project builds on earlier findings from our lab that functional cartilaginous tissue can be engineered using MSCs isolated from within the intrapatellar fat pad of the knee.

The ultimate aim is to develop a cell-based therapy that, from MSC isolation to construct implantation, could be undertaken within hours in the clinical setting.

We are also exploring an alternative therapy for cartilage defect repair.

Specifically, the objective is to engineer in the lab a tissue with a structure and composition that mimics that of normal articular cartilage using MSCs.

This is important because the mechanical functionality of articular cartilage is derived from its structure and composition.

By re-engineering fully functional cartilaginous grafts in vitro, it is hoped that tissue engineering therapies can be expanded to treat larger defects to the joint surface.

Treating these larger defects requires a more mechanically functional tissue as the graft will be fully load-bearing from the time of implantation.

This is a critical challenge that needs to be overcome if in the future we are to scale-up these approaches to engineer biological joint replacement prosthesis as a treatment/cure for OA.

Irish Independent Supplement

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