The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation
The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation
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DOI：
10.1016/j.biomaterials.2006.08.033
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发表时间：
2007-01-01
期刊：
影响因子：
14
通讯作者：
Anseth, Krish S.
中科院分区：
文献类型：
--
作者：
Benoit, Danielle S. W.;Durney, Andrew R.;Anseth, Krish S.
用肝素功能化的聚乙二醇（PEG）水凝胶被用作人间充质干细胞（hMSC）的三维培养系统。肝素功能化水凝胶支持 hMSC 活力（通过活/死成像进行量化），并诱导成骨分化（通过 5 周研究中碱性磷酸酶 (ALP) 产生以及骨桥蛋白 (OPN) 和胶原蛋白 I (COL 1) 基因表达的增加来测量）。进一步探讨了肝素诱导成骨分化的潜在机制。具体来说，控制培养系统中骨形态发生蛋白 2 (BMP2) 和纤连蛋白 (FN) 的可用性，并评估 hMSC 成骨分化作为微环境的函数。 BMP2 的可用性增加了 ALP 的产生和 OPN 基因的表达，而 FN 增加了 ALP 的产生，但不增加 OPN 基因的表达。此外，整合素表达的免疫染色显示，整合素产生对活力和分化有不同的影响，其中α5β1和αvβ3整合素-配体相互作用都支持活力，而只有α5β1整合素在hMSC成骨分化中发挥作用。 (c) 2006 Elsevier Ltd. 保留所有权利。
Poly(ethylene glycol) (PEG) hydrogels functionalized with heparin were utilized as a three-dimensional culture system for human mesenchyrnal stem cells (hMSCs). Heparin-functionalized hydrogels supported hMSC viability, as quantified through live/dead imaging, and induced osteogenic differentiation, as measured by increased alkaline phosphatase (ALP) production and osteopontin (OPN) and collagen I (COL 1) gene expression over the 5-week-study. Further exploration of the potential mechanism of heparin-induced osteogenic differentiation was performed. Specifically, the availability of bone morphogenetic protein 2 (BMP2) and fibronectin (FN) in the culture system was controlled and hMSC osteogenic differentiation was evaluated as a function of the microenvironment. BMP2 availability increased both ALP production and OPN gene expression, while FN increased ALP production, but not OPN gene expression. Furthermore, immunostaining of integrin expression revealed that viability and differentiation were differentially affected by integrin production, where both alpha 5 beta 1 and alpha v beta 3 integrin-ligand interactions supported viability, while only the alpha 5 beta 1 integrin played a role in hMSC osteogenic differentiation. (c) 2006 Elsevier Ltd. All rights reserved.