Abstract

Mesenchymal stem cells for cartilage regeneration

Zheng Yang, Principal Investigator, NUS Tissue Engineering Program, National University of Singapore

Adult articular cartilage is an avascular tissue that has limited self-regeneration capacity, and thus even minor injuries or lesions may lead to progressive damage and osteoarthritic joint degeneration. Current non-cell-based reparative procedures result mostly in healing with fibrocartilaginous tissue. Although culture-expanded autologous chondrocytes have been used to treat cartilage defects, the limited source of healthy donor cartilage and the low proliferative capacity has limited the use of autologous chondrocyte implantation (ACI), especially for critical size lesion. Cartilage tissue engineering using stem cells, in particular tissue-derived mesenchymal stem cells (MSC), offers a promising approach for cartilage repair due to their relative ease in extraction, high growth rate and ability to be differentiated into chondrocytes. Clinical trials have shown better arthroscopic and histological outcome for cartilage repair, compare to non-treatment control. A clinical cohort study comparing chondrocyte implantation in the treatment of articular cartilage lesions with cultured bone marrow derived MSCs has shown comparable clinical outcome. While significant advances have been made in the use of MSC, MSC-generated cartilage was not completely hyaline cartilage, yielding a neocartilage tissue with sub-optimal functional properties, predisposing the repaired cartilage to degeneration overtime. Despite efforts by researchers over the last two decades, achieving fully functional cartilage tissue repair remains a significant challenge. The complexity of this problem suggests that a multidisciplinary approach, combining a clinical perspective with expertise in cell biology, biomechanics, biomaterials science is needed to address the challenge of developing functional cartilage replacements.