Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue

Abstract

The ability of bone-marrow-derived mesenchymal stem cells (MSCs) and adipose-derived stem cells (ASCs) to undergo chondrogenic differentiation has been studied extensively, and it has been suggested that the chondrogenic potential of these stem cells differ from each other. Here, we provide a comprehensive review and analysis of the various growth factor induction agents for MSC and ASC three-dimensional in vitro chondrogenic differentiation. In general, the most common growth factors for chondrogenic induction come from the transforming growth factor beta (TGFbeta) superfamily. To date, the most promising growth factors for chondrogenesis appear to be TGFbeta-3 and bone morphogenetic protein (BMP)-6. A thorough review of the literature indicates that human MSCs (hMSCs) appear to exhibit the highest chondrogenic potential in three-dimensional culture in the medium containing both dexamethasone and TGFbeta-3. Some reports indicate that the addition of BMP-6 to TFGbeta-3 and dexamethasone further increases hMSC chondrogenesis, but these results are still not consistently supported. Induction of human ASC (hASC) chondrogenesis appears most successful when dexamethasone, TGFbeta-3, and BMP-6 are used in combination. However, to date, current formulations do not always result in stable differentiation to the chondrocytic lineage by hMSCs and hASCs. Continued research must be performed to examine the expression cascades of the TFGbeta superfamily to further determine the effects of each growth factor alone and in combination on these stem cell lines.