Effects of dual delivery of rhPDGF-BB and rhBMP-2 on osteogenic differentiation of human mesenchymal stem cells

The purpose of the study was to determine the effects of dual administration of recombinant human platelet derived growth factor-BB (rhPDGF-BB) and recombinant human bone morphogenetic protein-2 (rhBMP-2) on proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Either rhPDGF-BB or rhBMP-2 or a combination of the two factors was administered into hMSCs. Proliferation and osteogenic differentiation were determined by measuring DNA concentration, alkaline phosphatase (ALP) activity and mineralization (von Kossa staining) at days 7, 14 and 21. The data revealed that the administration of rhPDGF-BB (days 1-7) followed by rhBMP-2 (days 7-21) resulted in a significant increase of ALP activity and extracellular mineral deposition of hMSCs as compared to that of either factor alone or concurrent administration of the two factors. In addition, rhPDGF-BB treatment at days 1-7 significantly increased proliferation of hMSCs without decreasing osteogenic differentiation. The results underscored the importance of a coordinated, temporal sequence of rhPDGF-BB and rhBMP-2 administration to modulate hMSC osteogenic differentiation. The study was a compelling advancement towards producing a therapy exploiting temporal, dual administration of physiological doses of rhPDGF-BB and rhBMP-2.