April 5, 2007
Researchers develop economic system for expanding stem cells to form cartilage tissue
Knee osteoarthritis affects 30 million people worldwide, causing pain and joint stiffness and in severe cases restricted mobility. The limited ability of this tissue to repair itself means that surgical intervention is usually required and over 600,000 surgical procedures are performed each year in the US.
Professor Mohamed Al-Rubeai, currently a UCD Professor of Biochemical Engineering and principal investigator with the Centre for Synthesis and Chemical Biology and UCD Conway Institute has developed an economical tissue engineering approach which could offer new possibilities for restoring damaged or lost knee cartilage tissue.
One of the most successful therapies is cell transplantation which involves removing a patient's own mature cartilage cells known as chondrocytes and growing them in vitro using tissue culture techniques. Once the cells have multiplied the patient must then undergo a second surgical procedure for implanting them into the knee. The implanted chondrocytes will then help to produce healthy cartilage.
"There are a number of new transplantation products in clinical trials that all use chondrocytes," explains Professor Al-Rubeai. "However, these cells have limitations because when they divide they lose the potential to form cartilage and the overall treatment is expensive."
Tissue engineering using stem cells
While at the University of Birmingham, Professor Al-Rubeai with collaborators in the Smith & Nephew research centre decided to turn their attention to tissue culture techniques using adult stem cells, which retain their ability to form cartilage when grown in vitro and enable the generation of large cell banks.
"Routine tissue culturing methodologies cannot cope with the scale of cell production required to create world stem cell banks for engineering knee cartilage tissue," explains Professor Al-Rubeai.
His research group has optimised the tissue culture techniques so they can grow more stem cells in vitro which have the characteristics or morphology of in vivo stem cells.
"This is the first study to factor in economics. A key objective of our work is to develop a model for the biopharmaceutical industry by generating a cell bank using an affordable technique," continues Professor Al-Rubeai. "A 17-fold expansion factor was consistently achieved and large numbers of stem cells for tissue culture engineering were obtained."
Supporting stem cells
Once the stem cells are expanded the challenge is to engineer new cartilage tissue before implantation into the knee. To do this stem cells are supported on a bioactive scaffold which shapes the cells so they will provide a better match to the in vivo environment.
Engineers at the UCD School of Chemical and Bioprocess Engineering are now beginning to look at biodegradable gels to make a cartilage construct. These hydrogels can help form the new cartilage tissue and once implanted the gel will biodegrade.
"Presently we are using bovine stem cells but we would like to progress to using human stem cells," concludes Professor Al-Rubeai. "Our aim now is to collaborate with clinicians so we can move this work into the clinic."
Melero-Martin JM, Dowling MA, Smith M, Al-Rubeai M, Expansion of chondroprogenitor cells on macroporous microcarriers as an alternative to conventional monolayer systems, Biomaterials 2006, 27 (15): 2970-2979.