Adenosine Signaling Mediates Osteogenic Differentiation of Human Embryonic Stem Cells on Mineralized Matrices.
Adenosine Signaling Mediates Osteogenic Differentiation of Human Embryonic Stem Cells on Mineralized Matrices.
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DOI：
10.3389/fbioe.2015.00185
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发表时间：
2015
影响因子：
5.7
通讯作者：
Varghese S
中科院分区：
文献类型：
--
作者：
Rao V;Shih YR;Kang H;Kabra H;Varghese S
人胚胎干细胞（hESCs）因其自我更新和分化的能力而成为组织工程和再生医学中有吸引力的细胞来源。设计具有促进hESC向目标细胞类型分化的内在能力的生物材料在组织再生方面具有显著优势。我们之前已经开发出生物矿化磷酸钙（CaP）基质，其本质上直接引导hESCs的成骨分化，而不需要成骨诱导化学物质或生长因子。本研究表明，CaP基质驱动的hESCs成骨分化通过A2b腺苷受体（A2bR）发生。a2br特异性拮抗剂对受体的抑制可减弱矿化基质介导的hESCs成骨分化。此外，当在缺乏CaP矿物质的基质上培养时，外源性腺苷促进hESCs的成骨分化，但由于A2bR的抑制而减弱。这种本质上支持hESCs成骨承诺的合成基质不仅有利于骨组织工程，而且可以作为研究细胞外环境的物理和化学线索对干细胞承诺的影响的平台。对基质诱导的干细胞分化过程中细胞信号传导的深入了解也将有助于定义关键过程，并有助于发现促进骨组织工程多能干细胞分化的新靶点。
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 biomaterials with an intrinsic ability that promotes hESC differentiation to the targeted cell type boasts significant advantages for tissue regeneration. We have previously developed biomineralized calcium phosphate (CaP) matrices that inherently direct osteogenic differentiation of hESCs without the need of osteogenic-inducing chemicals or growth factors. Here, we show that CaP matrix-driven osteogenic differentiation of hESCs occurs through A2b adenosine receptor (A2bR). The inhibition of the receptor with an A2bR-specific antagonist attenuated mineralized matrix-mediated osteogenic differentiation of hESCs. In addition, when cultured on matrices in an environment deficient of CaP minerals, exogenous adenosine promoted osteogenic differentiation of hESCs, but was attenuated by the inhibition of A2bR. Such synthetic matrices that intrinsically support osteogenic commitment of hESCs are not only beneficial for bone tissue engineering but can also be used as a platform to study the effect of the physical and chemical cues to the extracellular milieu on stem cell commitment. Insights into the cell signaling during matrix-induced differentiation of stem cells will also help define the key processes and enable discovery of new targets that promote differentiation of pluripotent stem cells for bone tissue engineering.