UC San Diego

Human embryonic stem cells (hESCs) are attractive cell sources for tissue engineering and regenerative medicine due to their self-renewal and differentiation ability. Design of simple biomaterials with an intrinsic ability that facilitates hESC differentiation to the targeted cell type boasts significant advantages for tissue regeneration. We have previously developed biomineralized matrices that promote osteogenic differentiation of hESCs without the need of osteogenic-inducing soluble factors. In this study, we investigate the signaling involved and identify a role of the A2b adenosine receptor (A2bR) during the differentiation process. Our findings show that mineralized matrix-driven osteogenic differentiation occurs through A2bR as inhibition of the receptor attenuated this process. In addition, when cultured on matrices in an environment deficient of calcium phosphate (CaP) minerals, exogenous adenosine promoted osteogenic differentiation of hESCs and this was diminished through the use of an A2bR-specific antagonist. Such synthetic matrices that intrinsically support osteogenic commitment of hESCs are beneficial for cell-based tissue engineering. Insights into the cell signaling during differentiation will help define the key processes and enable the design of novel biomaterials that actively promote cell differentiation for bone tissue engineering