Effect of the Bone Morphogenetic Protein-2 Doses on the Osteogenic Potential of Human Multipotent Stromal Cells- Containing Tissue Engineered Constructs

Abstract : The addition of bone morphogenetic protein-2 (BMP-2) with multipotent stromal cells (MSC) is an attractive strategy to enhance the bone-forming potential of MSC-based tissue engineering (TE) constructs. However, the effective dosage of BMP-2 remains to be determined. In this study, we evaluated the effects of human MSCs codelivered with BMP-2 at either low or high dosage on the bone-forming potential of constructs in a mice ectopic model. Our results showed that the addition of only low dose of BMP-2 was beneficial to enhance the bone-forming potential of MSCs, whereas high dose of BMP-2 overcame the advantage of combining this growth factor with MSCs. Expressions of select genes of both murine and human origins in TE constructs demonstrated that the beneficial effect of low dose of BMP-2 with implanted human MSCs did not involve enhanced differentiation of these cells into osteoblasts or induction of paracrine cues but rather involved induction of the osteogenic differentiation of the host progenitors. Therefore, the advantage of combining BMP-2 with MSCs to enhance the bone-forming potential of TE constructs appeared to be an additive effect of both components rather than a synergistic one.