Osteoarthritis is the most common form of arthritis affecting more than 20 million Americans. It is one of the leading causes of disability and loss of freedom. The purpose of this article is to discuss the science behind some of the new developments in tissue engineering.
The gristle that caps the ends of long bones and which is responsible for cushioning joints is called cartilage. The only cell type within cartilage is the chondrocyte. Chondrocytes are responsible for producing and maintaining the environment around them which is called the extracellular matrix.
While water makes up about 80 per cent of the weight of the extracellular matrix, proteins are the major building blocks within the cartilage extracellular matrix.
Three classes of proteins exist in articular cartilage: collagens; proteoglycans; and other non-collagen proteins. Each protein component has an electrical charge associated with it. The interaction between highly negatively charged cartilage proteoglycans and collagen is responsible for both the ability of cartilage to sustain loads as well as to resist various stresses.
Osteoarthritis occurs as a result of dysfunction of this highly regulated system. The end result is gradual loss of the tensile and load-bearing capabilities of cartilage. This leads to cartilage damage and subsequent wear and tear. Cartilage has limited ability to repair itself once damage has occurred.
The treatment for osteoarthritis until recently has been primarily aimed at symptom control. Palliation of pain and improvement in function have been the goals. Various treatments such as analgesics, non-steroidal anti-inflammatory drugs, physical therapy, glucocorticoid ("cortisone") injections, and injections of viscosupplements can provide a modicum of symptom relief.
However, the "end game" has been the resultant need for surgical solutions such as total joint replacement with all its attendant risks and complications.
Recently, there has been interest in the role of tissue engineering... the ability to regenerate new cartilage.
Two major methods have been studied. In one, cartilage has been grown outside the body in a laboratory and then, once fully functional, has been re-implanted into the joint. In the other, cells capable of becoming cartilage are implanted without being cultured outside the body and allowed to mature inside the joint.
Common to both techniques is the need for three critical components. The components are: cells capable of becoming cartilage, a scaffold or matrix to help support cell growth, and finally a suitable environment that enhances growth.
An example of the first technique- growing cartilage cells outside the body first and then re-implanting the cells- is the Carticel簧 method.
Carticel, a procedure patented by Genzyme, is the only FDA-approved cell-based cartilage repair process in the US. In this method, cartilage is harvested from a non-weight bearing part of the joint. The cartilage is then prepared in a manner so that the chondrocytes are teased from the extracellular matrix, and are allowed to multiply in a laboratory setting. After enough cartilage cells have been grown, they are then implanted into the area of cartilage damage.
Long term results of this technique, which is limited to small isolated areas of cartilage damage, have not been as encouraging as once thought.
A more attractive approach has been the use of mesenchymal stem cells. These cells can multiply, divide, and differentiate very well when provided with a suitable matrix and environment (growth factors).
Mesenchymal stem cells can be found in the bone marrow, fat, bone, joint lining, muscle, and other tissues. When stimulated by growth factors, mesenchymal stem cells will become active in the repair process. The growth factors include but are not limited to insulin-like growth factor, transforming growth factors, bone morphogenic protein, and fibroblast growth factors.
Another interesting phenomenon is the ability of certain stressors such as joint loading and shearing to stimulate mesenchymal stem cell growth and differentiation.
Work from Dr. Rocky Tuan and his colleagues at the National Institutes of Health and the University of Pittsburg has helped elucidate some of the complexities involved in this process.
As with all new scientific developments, there are more questions than answers. What is the best matrix? How should it be harvested? How should it be implanted? What other growth factors might be effective in stimulating mesenchymal stem cell growth and differentiation? What is the appropriate procedure to use to introduce all of the above? What are the long term benefits? What are the long term pitfalls?
The answers to these pressing issues are being addressed. A new era of tissue regeneration holds much promise for the definitive treatment of osteoarthritis.
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