Extracellular matrix protein adsorption to phosphate-functionalized gels from serum promotes osteogenic differentiation of human mesenchymal stem cells.
Extracellular matrix protein adsorption to phosphate-functionalized gels from serum promotes osteogenic differentiation of human mesenchymal stem cells.
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DOI：
10.1016/j.actbio.2012.09.007
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发表时间：
2013-01
影响因子：
9.7
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Gandavarapu, Navakanth R.;Mariner, Peter D.;Schwartz, Michael P.;Anseth, Kristi S.
组织工程的主要目标之一是通过刺激特定细胞功能诱导新组织形成。人间充质干细胞（hMSCs）是一种特别重要的细胞类型，已被广泛研究用于分化成骨（骨）谱系，我们最近发现，简单的磷酸盐官能团纳入聚（乙二醇）水凝胶可以诱导成骨，而不使用分化培养基通过未知的机制。在这里，我们的目的是确定是否直接或间接的细胞/材料的相互作用是负责指导hMSCs的成骨谱系磷酸盐（PO 4）功能化的聚（乙二醇）（PEG）水凝胶。我们的研究结果表明，血清组分吸附到PO 4-PEG水凝胶从媒体中的预浸泡步骤是足够的附着和扩展的hMSCs，即使在无血清条件下接种。胶原蛋白和纤连蛋白的阻断抗体（靶向水凝胶）以及β1和β3整联蛋白阻断抗体（靶向细胞）均降低了hMSC与PO 4-PEG水凝胶的附着，表明细胞与吸附的基质组分之间的整联蛋白介导的相互作用促进了附着和扩散。在信号传导之外，而不仅仅是形状变化，被发现是骨生成所需的，因为碱性磷酸酶（ALP）活性和CBFA 1、骨桥蛋白和胶原蛋白-1的表达在抑制粘着斑激酶（FAK）磷酸化后均显著下调，即使粘着斑结构或细胞形状不变。我们的结果表明，复杂的功能（即，成骨分化）可以使用简单的功能化策略（例如引入PO 4）来控制，但是这些材料的作用可能是由于比以前认识到的更复杂的影响。
One of the primary goals for tissue engineering is to induce new tissue formation by stimulating specific cell function. Human mesenchymal stem cells (hMSCs) are a particularly important cell type that has been widely studied for differentiation down the osteogenic (bone) lineage, and we recently found that simple phosphate functional groups incorporated into poly(ethylene glycol) hydrogels could induce osteogenesis without using differentiation medium by unknown mechanisms. Here, we aimed to determine whether direct or indirect cell/materials interactions were responsible for directing hMSCs down the osteogenic lineage on phosphate (PO4) functionalized poly(ethylene glycol) (PEG) hydrogels. Our results indicated that serum components adsorbed onto PO4-PEG hydrogels from media in a pre-soaking step were sufficient for attachment and spreading of hMSCs, even when seeded in serum-free conditions. Blocking antibodies for collagen and fibronectin (targeted to the hydrogel), as well as β1 and β3 integrin blocking antibodies (targeted to the cells), each reduced attachment of hMSCs to PO4-PEG hydrogels, suggesting that integrin-mediated interactions between cells and adsorbed matrix components facilitate attachment and spreading. Outside in signaling, and not merely shape change, was found to be required for osteogenesis, as alkaline phosphatase (ALP) activity and expression of CBFA1, osteopontin and collagen-1 were each significantly down regulated upon inhibition of focal adhesion kinase (FAK) phosphorylation even though focal adhesion structure or cell shape were unchanged. Our results demonstrate that complex function (i.e.,osteogenic differentiation) can be controlled using simple functionalization strategies, such as incorporation of PO4, but that the role of these materials may be due to more complex influences than has previously been appreciated.
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影响因子：
3.7
作者：
Lin CC;Anseth KS
通讯作者：
Anseth KS
影响因子：
14
作者：
Curran, Judith M.;Chen, Rui;Hunt, John A.
通讯作者：
Hunt, John A.
影响因子：
14
作者：
Allen, LT;Tosetto, M;Gallagher, WM
通讯作者：
Gallagher, WM
影响因子：
3.4
作者：
Brizuela Guerra, Nayrim;Gonzalez-Garcia, Cristina;Salmeron-Sanchez, Manuel
通讯作者：
Salmeron-Sanchez, Manuel
DOI：
10.1002/jbm.820270816
发表时间：
1993-08-01
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子：
--
作者：
IULIANO, DJ;SAAVEDRA, SS;TRUSKEY, GA
通讯作者：
TRUSKEY, GA