Monday, November 15, 2010

Multiplying stem cells

By K.M. LEW
A researcher discovers a technique that might make it easier and cheaper to replace worn-out cartilage.

     HAVE your knees started to creak? If your joints are beginning to make crackling noises when you bend them, this may be a sign that the cartilage there is starting to wear out.
     As cartilage acts as a cushion to soften the impact of movements on our joints, this is not a good sign. Imagine your bones grinding together every time you move – definitely a painful proposal!
     Unfortunately, as we grow older, our cartilage wears out through repeated usage. And that is the inspiration behind Universiti Malaya (UM) research scientist Chong Pan Pan’s current work.

Important discovery: Dr Chong Pan Pan found a way to separate mesenchymal stem cells from blood, and growing them in the laboratory.
     “As we know, most people have knee problems when they are older, that is osteoarthritis. So I wanted to find something to help solve their problems,” she says.
     The PhD student, who is attached to the Tissue Engineering Group in the Medical Faculty’s Department of Orthopaedic Surgery, has come up with a method to increase the number of mesenchymal stem cells available from a patient’s blood.

New method

     Mesenchymal stem cells are a type of pluripotent stem cell that have the ability to differentiate into various types of cells that make up our blood and connective tissues (refer to Hierarchy of stem cells). This includes chondrocytes, which are the cells that form cartilage.
     In adults, stem cells are usually taken from the bone marrow. However, there is also a small amount of these cells floating around in our blood. The problem is the number of stem cells available from blood is too small to be of practical use.
     What Chong has discovered is a method of separating the mesenchymal stem cells from the rest of the blood, and growing them in the laboratory.
     According to her, this means that from a mere 2ml of blood, she can obtain around one million mesenchymal stem cells, of which 90% can be differentiated into chondrocytes.
     Although the number of cells needed for cartilage repair depends on the size of the defect, Chong estimates that a small defect would probably require around 10-20 million mesenchymal stem cells.
     “My advantage is that I can shorten the differentiation time,” she says. “It usually takes about three to four weeks, but I’ve managed to shorten it to two weeks.”
     Currently, the cell-based treatment procedure for damaged knee cartilage, known as an autologous chondrocyte implantation, requires two operations.
    The first one is to allow healthy cartilage to be harvested from the patient’s knee using an athroscope. These cells are then cultured and grown in the laboratory until they reach the amount needed to cover the damaged area. This usually takes around four to six weeks.
     The second operation is to place these healthy cells onto the damaged area, where they are suppose to grow into new cartilage.
     But Chong says: “Autologous transplantation works only if you still have cartilage left (to transplant). If not, you have to do a total knee replacement.”
     While using mesenchymal stem cells from bone marrow also requires two surgical procedures – the first to harvest the stem cells from the bone marrow, and the second to place them on the damaged area – the advantage is that the harvesting procedure costs less and the knee only needs to undergo one procedure.
     According to Chong, 2ml of bone marrow can produce around three million mesenchymal stem cells.
     Although this is more than what even her new method of growing stem cells from blood can produce, the advantage in her method lies in the fact that the drawing of blood from patients is a simple and cheap procedure.
     It also means that patients would only need to undergo one operation to place the new stem cells onto the damaged area.

A long way to go

     But Chong cautions that her technique is just moving into the animal testing stage.
     “To get to the patient, there are three stages: the fundamental research work, immuno-animal studies, and the clinical trials.
     “My colleagues in the Tissue Engineering Group have just started the immuno-animal testing,” she explains.
     She says that this stage will take one to two years as the researchers will have to take time to see if the blood-derived stem cells can repair cartilage damage after transplantation, as well as to observe if there are any side effects from the procedure.
     “Clinical trials (in human patients) will also take another one to two years. So, the fastest we can introduce this to patients would be within three to five years,” she says.
     She adds that if the trials go well and receives the appropriate approval, this treatment method will be offered at the UM Medical Centre.
     While Chong hopes that her technique will help to phase out the need for total knee replacements in the future, she adds that only hospitals with laboratory facilities will be able to provide this method of treatment.
     “Cell-based therapy like this needs lab facilities, and you need to involve scientists to prepare the cells for culture and growth,” she says.
     In the meantime, she is in the process of patenting her technique, as well as continuing her research work and PhD studies.
     Currently, she is researching methods to revert mesenchymal stem cells back to pluripotent stem cells, so that a source of these cells – which can differentiate into almost any of the specialised cells in our body – will be readily available in our own bodies for future therapeutic use.

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