Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6

Objective. Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adipose-derived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor beta 1 (TGF beta 1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type 11 collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGF beta 1, TGF beta 3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads. Methods. The chondrogenic response of alginate-encapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3 H-proline and 35 S-sulfate incorporation, and immunolabeling for specific extracellular matrix components. Results. Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 upregulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COLIOAI expression by similar to 2-fold. Conclusion. These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.