Adult Stem Cells for Cartilage Regeneration

Abstract

As cartilage is an avascular, aneural structure, it has very low capabilities of self-repair. Osteoarthritis prevalence is increasing, and there are no clinically approved management techniques that can cure the degradation of cartilage. This report investigates the efficacy of different sources of cells to generate articular cartilage. Autologous chondrocyte implantation has been used to some extent in clinics; however it has not generated efficient, reliable results, and there is no evidence of long-term success. The usage of stem cells is more promising, particularly mesenchymal stem cells (MSCs). Human embryonic stem cells (hESCs) have also been trialed; however, it is important to note that the process of differentiation into chondrocytes is not fully understood, and the cartilage produced can often be of poor quality. MSCs seems to be the way forward, and hESCs will perhaps need further study with the usage of MSC differentiation methodology.

Keywords: chondrogenic cells; collagen degradation; human embryonic stem cells; mesenchymal stem cells (mscs); osteoarthritis.

Figure 1. Schematic representation of articular cartilage

Schematic representation of articular cartilage. The networks of collagen are evident, as is the aggrecan aggregation with hyaluronan and link protein. Adapted from [1] with permission.

Figure 2. Chondrogenesis of MSCs in vivo and in vitro.

(a) In vivo chondrogenesis. (a.i) Chondrogenesis begins during embryonic development with MSCs expressing collagen I. (a.ii) MSCs migrate and form mesenchymal condensations which activate molecular signalling cascades from plasma membrane receptors, including N-CAM and N-Cadherin. (a.iii) MSCs then proceed to undergo chondrogenic differentiation, depositing cartilage-ECM molecules (such as CD44, collagen II and aggrecan) under the influence of SOX9. (b) In vitro chondrogenesis. (b.i) MSCs are aggregated ex vivo in a 2D-monolayer. (b.ii) MSCs are then added to a 3D-cell aggregate and are grown in this medium. Following this, in vitro differentiation is then the same as in vivo. Adapted from [10] with permission.