Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6

Recent interest has focused on mesenchymal stem cells (MSC) for tissue engineering and regenerative therapy of cartilage defects. MSC originating from adipose tissue (ATSC) are attractive as they are easily available and abundant. They have similar properties like bone marrow derived MSC (BMSC), except for a reduced chondrogenic potential under standard culture conditions driven by TGFbeta. Aim of this study was to search for possible differences explaining the reduced differentiation capacity of ATSC and to eliminate it by adaptation of induction protocols. Expanded MSC were analyzed for their growth factor and related receptor repertoire and ATSC spheroid cultures were supplemented with BMP-2,-4,-6,-7, TGFbeta, FGFa, FGFb, IGF-1, and PTHrP alone or in combination with TGFbeta. In contrast to BMSC, ATSC showed reduced expression of BMP-2, -4, and -6 mRNA and did not express TGFbeta-receptor-I protein. Consistent with this, increased concentrations of TGFbeta did not improve chondrogenesis of ATSC. BMP6 treatment induced TGFbeta-receptor-I expression and combined application of TGFbeta and BMP-6 eliminated the reduced chondrogenic potential of ATSC inducing a gene expression profile similar to differentiated BMSC. Like in BMSC, chondrogenesis of ATSC was associated with hypertrophy according to premature collagen Type X expression, upregulation of alkaline-phosphatase activity and in vivo calcification of spheroids after ectopic transplantation in SCID mice. In conclusion, a distinct BMP and TGFbeta-receptor repertoire may explain the reduced chondrogenic capacity of ATSC in vitro, which could be compensated by exogenous application of lacking factors. Further studies should now be directed to induce chondrogenesis in the absence of hypertrophy.