Limited but heterogeneous osteogenic response of human bone marrow mesenchymal stem cells to bone morphogenetic protein-2 and serum

Abstract

Although there are numerous reports describing the in vivo bone forming capability of recombinant human bone morphogenetic proteins-2 (rhBMP-2), studies have reported limited effects on human mesenchymal stem cells (hMSCs). However, the reasons for these discrepancies are not well understood. The aim of this study was to investigate the responsiveness of hMSCs to osteoinductive signals, focusing on rhBMP-2 and the effect of serum on that responsiveness. Human MSCs from six donors were analysed. When those cells were treated with osteoinduction medium including dexamethasone (Dex), alkaline phosphatase (ALP) activities increased in all cell lines. On the other hand, rhBMP-2-containing medium failed to increase ALP activity. When five different sera were used for cultivation and induction with rhBMP-2, ALP activities increased in two of them, but not in the others. The expression of BMP-2 antagonist noggin was induced in almost all combinations regardless of the responsiveness to rhBMP-2. On the other hand, the expression of follistatin showed significant variations depending on the serum and cell line. However, the expression did not correlate with the responsiveness to rhBMP-2. The results from this study showed limited but heterogeneous osteogenic response of hMSCs to rhBMP-2 and that the results are affected by the choice of serum. This fact should be concerned for the successful and effective clinical application of rhBMP-2.

Keywords::

• Bone regeneration
• tissue engineering
• mesenchymal stem cells
• BMP-2
• ALP activity

Acknowledgements

This work was supported in part by a grant for “Research on Human Genome and Tissue Engineering” from the Ministry of Health, Labor and Welfare of Japan, a Japanese Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science, and by a Grant-in-aid for “Young Scientists (start up)” (20890100) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.