讲座题目:A Comprehensive Translational Study of Autologous Bone-marrow Derived Stem Cells for Cartilage Disease: A Singapore Update
报告人:Dr. James Hui Hoi Po
时 间:6月4日(周五)下午4:00
地 点:廖凯原楼2-102会议室
主持人:葛子钢(特聘研究员)
报告内容摘要:
The knee is the most important joint in humans and its disorders usually affect the quality of life. Knee-related disorders include chondral injuries, meniscus tears and cruciate ligament injuries. Current treatments for these disorders can be improved upon.
At present, techniques in the biological resurfacing of cartilage defects require an open arthrotomy and involve the direct transplantation of isolated cells and/or scaffolds, or whole tissue grafts with chondrogenic potential onto the cartilage defects. Our preliminary study demonstrated the effect of direct intra-articular injection of mesenchymal stem cells suspended in hyaluronic acid as an alternative to the much more invasive methods currently available.
Removal of the meniscus is the only useful method for the treatment of the lesions in the avascular meniscus. The loss of the meniscus results in an abnormal load transmission to the knee, therefore making the patient predisposed to osteoarthritis. Our study investigated the use of mesenchymal stem cells to enhance the repair of meniscal tears in the avascular zone in a porcine model. Histological examination of the experimental group revealed healing with fibrocartilage-like tissue resulting in a stronger biomechanical repair.
Poor osteo-integration at the tendon tunnel junction leads to graft laxity in the current technique of hamstring tendon reconstruction of anterior cruciate ligament. Our study showed that Coating of tendon grafts with MSCs results in healing by an intervening zone of cartilage resembling the chondral enthesis of normal ACL insertions, rather than by collagen fibers and scar tissue. MSC-enhanced ACL reconstructions perform significantly better than controls on biomechanical testing.
In our preliminary study of chondrogenesis of MSCs, bone marrow MSCs were found to be superior to adipose derived stem cells in their ability to secrete more GAG and Collagen type II. We have also demonstrated that chondroitin sulphate is a powerful supplement in regulating chondrocyte proliferation and adhesion in a dose-dependent increase at a concentration of up to 10 000 ng/ml of proliferation and migration. Real-time PCR analysis revealed the regulation of collagen II in chondrocytes.
An ideal polymer for tissue engineering application must offer a high degree of customization to suit specific requirements, and this is particularly so in cartilage tissue engineering. In this case, the scaffold material must be degradable, possess good mechanical toughness even at high porosity, and have the ability to transfer load from the scaffold to the host tissues during healing and re-modeling. In addition, it must be capable of delivering bioactive molecules to enhance healing, and can also be used in situ as a gel. Nanomesh and PCL stem cell constructs were recently shown to be effective in regenerating cartilage defects.
We are carrying out a study of Hydrogel-encapsulated and CS-enhanced MSCs to be injected intra-articularly on the porcine model of various injured tissues sites. These include cartilage defects in the knee joints, meniscal tears in the avascular zone and anterior cruciate ligament ruptures.