The Potential of Human Embryonic Stem Cells for Articular Cartilage Repair and Osteoarthritis Treatment

Abstract

Osteoarthritis is a debilitating joint disease present in epidemic proportions worldwide. Osteoarthritis results from degeneration of the articular cartilage of the joint surfaces due to acute trauma, or chronic wear and tear. Due to limited ability of cartilage to repair itself, and lack of available treatments, there is an urgent need for development of approaches to repair articular cartilage damage due to injury or osteoarthritic disease. Cell-based repair strategies are among the most promising of these approaches. Various adult cell sources for cartilage repair are proposed including autologous adult chondrocytes as well as adult Mesenchymal Stem Cells (MSC). Disadvantages such as destructive harvest protocols; poor proliferation, and particularly for MSC, considerable cellular heterogeneity, have limited success of these cell types for cartilage repair. Chondrogenic cells derived from human embryonic stem cells(hESC) offer a highly proliferative cell source, which when directed into the chondrogenic lineage, could provide an ideal source of cells for cartilage repair. Chondrogenic cells derived from human induced pluripotent stem cells(iPSC) offer additional advantages for patient-specific therapy. Recently protocols have been established for directed differentiation of hESC into the chondrogenic lineage. Harnessing the potential of hESC-derived chondrogenic cells will require comprehensive testing of their efficacy for in vivo cartilage repair, as well as considerations of safety and immunogenicity of the cells. Use of pro-chondrogenic factors and/or bioactive scaffolds may assist in optimizing cartilage repair by chondrogenic cells. Repair of cartilage damage in osteoarthritis is a special challenge because of the widespread damage and presence of signals and stressors which disrupt normal joint homeostasis. Particular promise in cell-based repair of osteoarthritis may be provided by chondrogenic progenitor cells which may mimic endogenous repair responses. This review discusses the current status of cell-based cartilage repair strategies and in particular the potential role of hESC-derived chondrocytes or chondroprogenitor cells for treatment of articular cartilage damage due to injury and osteoarthritis.