Wednesday, October 2, 2013

Arthritis Treatment: Mesenchymal Stem Cells And Growth Factors For Osteoarthritis


As population demographics change with a gradually aging population, certain chronic diseases have become more common. There is a confluence of factors though that will make the management of chronic disease assume a greater level of importance. This is because not only are people living longer but they are maintaining a level of activity far greater than their parents and grandparents. This is most evident in the management of osteoarthritis where the incidence of joint replacement surgery is skyrocketing as Boomers demand a lifestyle which their forebears could only dream about.

Osteoarthritis (OA) is the most common form of arthritis and affects more than 20 million Americans. It is a condition that adversely affects hyaline articular cartilage, the smooth tough gristle that caps the ends of long bones.

Hyaline cartilage consists of two components: a matrix made up of a combination of proteoglycans (complexes of proteins and sugars), and chondrocytes. Chondrocytes are cartilage cells that manufacture matrix under normal healthy circumstances. They are responsible for nourishing the matrix as well.

With the development of OA, a distinct change in the joint environment occurs. Chondrocytes begin to elaborate destructive enzymes causing cracks and fissures in the cartilage. These are called "fibrillations." A complex interplay of events involving cartilage, bone, and synovium- the lining of the joint- then begins to snowball.

One of the most common joints affected by osteoarthritis is the knee. This is not a surprise since OA preferentially attacks weight-bearing joints.

Between symptomatic treatment and joint replacement surgery is a large gap in treatment measures. One area of recent interest is the use of mesenchymal stem cells (MSCs) in the management of OA. MSCs are the body's own stem cells which are found in many areas including bone marrow and fat. MSCs have the ability to differentiate into connective tissue of which cartilage is a prime example. Other types of connective tissue that MSCs have been shown to develop into are tendon, ligament, muscle, nerve, and intervertebral disc.

MSCs are active in the repair process when any type of connective tissue is injured. In degenerative disease like OA, the ability of stem cells may be depleted with less ability to differentiate and multiply. Animal studies have demonstrated that supplying additional MSCs may overcome this problem leading to healing and cartilage regeneration.

At least one human study in a small number of patients with OA of the knee has shown promising results using MSCs derived from bone marrow and fat. (Wei N, Beard S, Delauter S, Bitner C, Gillis R, Rau L, Miller C, Clark T. Guided Mesenchymal Stem Cell Layering Technique for Treatment of Osteoarthritis of the Knee. J Applied Res. 2011; 11: 44-48)

Combining MSCs with autologous growth factors found in platelet-rich plasma also has added a boost to the natural abilities of stem cells to multiply and divide.

Multiple centers now are applying these principles.

What most centers lack though is the knowledge of what initiates stem cell multiplication and division.

MSCs are stimulated to "go into action" when the critical initiating event, injury is initiated. Injury is what attracts stem cells and injury is what leads to the release of growth factors from platelets. That is why induction of injury by removal of osteophytes, scarification of bare bone, and fenestration of cartilage defects is absolutely crucial for cartilage regeneration to occur.

This is best done using a combination of arthroscopic and ultrasound guidance means.

In addition, providing the proper environment for the MSCs to thrive afterwards is also critical. The osteoarthritic joint is a hostile environment. Multiple measures need to be instituted so that proper survival of MSCs occurs. Institution of effective scaffolding is critical.

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