Saturday, November 30, 2013

More on the Science of Stem Cells for Osteoarthritis Treatment


Although they originally come from bone marrow, adult (or as they are often called, "mesenchymal") stem cells can be derived from a variety of body tissues. These tissues include fat, the thin lining on the surface of bone called the periosteum, joint lining (synovium), muscle, skin, baby teeth, and cartilage.

Their purpose is simply to act as repairmen to replace and regenerate cells that are lost as a result of injury, normal turnover, and aging. Think of them as the handyman around the house!

There have been attempts at defining exactly what constitutes a true mesenchymal stem cell. Various cell surface markers have been used to describe these cells and mesenchymal stem cells (MSCs)appear to share certain traits and characteristics in common. Finally, it has been agreed that a true MSC is capable of differentiating into bone, cartilage, as well as fat.

Although MSCs harvested from different tissues look the same, it's not clear if they behave the same or have the same capabilities.

One study, for instance, showed that the MSCs most able to become cartilage were stem cells derived from joint lining (synovial) tissue. Other MSCs that showed a good ability to become cartilage were those from bone marrow and from periosteum.

Another issue is quality of MSCs. How effective will they be under different circumstances? It's clear that stem cells placed in an environment with certain stimulatory growth factors differentiate better. On the flip side, there have been some studies indicating that advanced age may slow stem cell multiplication and division. However, other studies indicate that regardless of age, enough good quality MSCs can be obtained that do have adequate potential to differentiate into cartilage cells. (At our center, we usually use 75 years of age as our cutoff, although a few of our best results have occurred in older individuals.)

The potential application of MSCs to differentiate into cartilage cells and be used to repair cartilage damage in osteoarthritis is a hot topic nowadays.

It is a very complicated process though, and current research has used normal cartilage as the model to emulate. Most stem cell research models of cartilage have a few things in common. First, they use MSCs. Then, a matrix or scaffold is incorporated. This framework serves as a "home" for the MSCs. Finally, the stem cells are exposed to a variety of growth factors used to stimulate differentiation and multiplication.

In many experiments done in laboratory settings, the quality of cartilage derived from MSCs has been disappointing. It appears that the both the quality of stem cell as well as the extracellular environment is critical for the normal development of viable strong cartilage. The exact "key" remains elusive. There appears to be a complex interplay between enzymes and proteins that degrade cartilage such as matrix metalloproteinases and factors that build cartilage such as transforming growth factors, bone morphogenic protein, and parathyroid hormone, to name a few.

One final interesting point is that MSCs have a unique property that is often overlooked. They have immunosuppressive and anti-inflammatory functions that have been demonstrated both in the laboratory setting as well as in animal models. This has a lot of potential impact, particularly when considering their use in arthritis treatment.

For a more scientific discussion of the intricacies of MSC biology as it pertains to cartilage regeneration, readers are referred to the excellent works written by Drs. Faye Chen and Rocky Tuan.

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