Osteoarthritis: Are Stem Cells Really the Answer?

by Nathan Wei

Posted on Thursday 8th of January 2009


Osteoarthritis (OA) is the most common form of arthritis. It is characterized by degeneration of the articular cartilage (the gristle that caps the end of long bones in a joint) and, ultimately, joint destruction. OA is a major cause of disability in older adults and the prevalence of the condition is expected to increase over the next 20 years with the graying of the population. In fact, it has been estimated that more than 100, 000o Americans cannot transfer from their bed to the bathroom as a result of osteoarthritis of the hip or knee.

The burden of OA is made worse by the inadequacies of current therapies.

Non drug and various drug treatments are used for early OA, but protection of articular cartilage has so far not been available. Surgical intervention- meaning joint replacement- is often indicated when the symptoms cannot be controlled and the disease progresses.

Because this is such a significant public health problem- ranking among the top ten diseases chronic diseases impacting society- it has been an attractive target for researchers as well as clinicians specializing in arthritis.

A potentially valuable tool has been multipotent adult mesenchymal stem cells (MSCs), obtained from the bone marrow of normal adults. Many strategies have been studied and developed to possibly harness the ability of MSCs to differentiate into cartilage cells.

Osteoarthritis is a complicated disease. Cartilage cells, called chondrocytes, produce and secrete enzymes, such as matrix metalloproteinases and aggrecanases, which corrode cartilage.

Interleukin 1 (IL-1) is an inflammatory chemical messenger which makes these enzymes cause more damage. Stimulation of these factors leads to damage to cartilage through both reduced synthesis as well as accelerated breakdown. Other inflammatory messengers such as tumor necrosis factor are also involved in cartilage breakdown and, along with mechanical factors lead to worsening of the disease.

Despite much research into development of inhibitors of these molecules for use in treating OA, success with prevention of cartilage breakdown or with cartilage restoration has not been achieved.

That is why MSCs have been attractive. MSCs are cells that can be stimulated to differentiate along specific pathways, including cartilage production. In contrast to existing cartilage tissue which needs to be surgically harvested from non-weight-bearing cartilage, MSCs can be harvested from bone marrow.

Some evidence exists that tissue damage in osteoarthritis is due to depletion of MSC populations.

So why haven’t MSCs been used for OA treatment already?

First, questions exist as to whether MSCs obtained from patient with OA differ functionally from those of healthy people.

Also, age-dependent decline in the differentiation capability of MSCs has been reported by some investigators.

However, it should be pointed out that when MSCs are harvested and concentrated properly, enough MSCs with adequate differentiation potential can be isolated from patients with OA, irrespective of their age or the cause of their disease. These results indicate that MSCs for regeneration of cartilage in patients with OA is practical as well as feasible.

How to deliver stem cells is the biggest question. Direct into the joint injection of MSCs is, technically, the simplest approach to OA therapy. Unfortunately, there is no guarantee and even less data to support the effectiveness of this approach.

Compared with direct into the joint injection, MSC application to cartilage surfaces using a scaffold offers more control. The scaffold may consist of either natural or synthetic material. (The scaffold technique is the one advocated and used at the Arthritis and Osteoporosis Center of Maryland (301) 694-5800)

Another possible approach: MSCs can be introduced with various viral vectors. This permits delivery of genes that encode proteins that could potentially reverse some of the damage in OA.



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