Generating cartilage repair from pluripotent stem cells

Abstract

The treatment of degeneration and injury of articular cartilage has been very challenging for scientists and surgeons. As an avascular and hypocellular tissue, cartilage has a very limited capacity for self-repair. Chondrocytes are the only cell type in cartilage, in which they are surrounded by the extracellular matrix that they secrete and assemble. Autologous chondrocyte implantation for cartilage defects has achieved good results, but the limited resources and complexity of the procedure have hindered wider application. Stem cells form an alternative to chondrocytes as a source of chondrogenic cells due to their ability to proliferate extensively while retaining the potential for differentiation. Adult stem cells such as mesenchymal stem cells have been differentiated into chondrocytes, but the limitations in their proliferative ability and the heterogeneous cell population hinder their adoption as a prime alternative source for generating chondrocytes. Human embryonic stem cells (hESCs) are attractive as candidates for cell replacement therapy because of their unlimited self-renewal and ability for differentiation into mesodermal derivatives as well as other lineages. In this review, we focus on current protocols for chondrogenic differentiation of ESCs, in particular the chemically defined culture system developed in our lab that could potentially be adapted for clinical application.

FIG. 1.

Schematic diagram indicating some of the key factors that play roles in the differentiation of mammalian pluripotent epiblast cells progressively though a sequence of stages to generate chondrocytes.

FIG. 2.

The different pathways that have been exploited to differentiate human embryonic stem cells (hESCs) toward chondrocytes.

FIG. 3.

Schematic showing a breakdown of the defined protocol from our lab for directed differentiation of hESC to chondrogenic cells in three stages (modified from Oldershaw et al.).