Influence of select extracellular matrix proteins on mesenchymal stem cell osteogenic commitment in three-dimensional contexts.
Influence of select extracellular matrix proteins on mesenchymal stem cell osteogenic commitment in three-dimensional contexts.
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DOI：
10.1016/j.actbio.2012.07.048
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发表时间：
2012-12
影响因子：
9.7
通讯作者：
Hahn MS
中科院分区：
文献类型：
--
作者：
Becerra-Bayona S;Guiza-Arguello V;Qu X;Munoz-Pinto DJ;Hahn MS
生长因子已被证明是间充质干细胞（MSC）成骨分化的强大介质。然而，它们在组织工程支架中的使用不仅可能是昂贵的，而且可能在周围组织中诱导不期望的反应。因此，在不存在外源性生长因子的情况下，通过操纵支架材料性质特异性促进MSC成骨分化的能力将是有益的。目前的工作探讨了选择细胞外基质（ECM）蛋白对MSC成骨的影响，目标是开发具有内在骨诱导特性的支架。纤维蛋白原（FG）、纤连蛋白（FN）和层粘连蛋白-1（LN）因其在骨形态发生或骨折愈合中的已知作用而被选择用于评价。将这些蛋白质缀合到聚（乙二醇）二丙烯酸酯（PEGDA）水凝胶中，并评价其对包封的10 T1/2 MSC的影响。具体而言，培养1周后，检查各种MSC谱系的中期标志物，以评估观察到的成骨反应的强度和特异性。PEG-LN凝胶显示成骨转录因子osterix的水平相对于第0天水平增加。此外，相对于PEG-FN凝胶和第0天，PEG-FG和PEG-LN凝胶与骨ECM蛋白骨钙素沉积增加相关。重要的是，与FG和LN相关的成骨反应似乎是特异性的，因为在这些凝胶中，软骨细胞、平滑肌细胞和脂肪细胞谱系的标志物相对于第0天没有类似地升高。为了深入了解观察到的分化结果背后的整合素动力学，评估了细胞整合素谱的初始整合素粘附和时间变化。相关结果表明，α2，αv和α6整合素亚基可能在整合素介导的成骨中发挥关键作用。
Growth factors have been shown to be powerful mediators of mesenchymal stem cell (MSC) osteogenic differentiation. However, their use in tissue engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically promote MSC osteogenic differentiation in the absence of exogenous growth factors via manipulation of scaffold material properties would be beneficial. The current work examines the influence of select extracellular matrix (ECM) proteins on MSC osteogenesis toward the goal of developing scaffolds with intrinsically osteoinductive properties. Fibrinogen (FG), fibronectin (FN), and laminin-1 (LN) were chosen for evaluation due to their known roles in bone morphogenesis or bone fracture healing. These proteins were conjugated into poly(ethylene glycol) diacrylate (PEGDA) hydrogels and their effects on encapsulated 10T½ MSCs were evaluated. Specifically, following 1 week of culture, mid-term markers of various MSC lineages were examined in order to assess the strength and specificity of the observed osteogenic responses. PEG-LN gels demonstrated increased levels of the osteogenic transcription factor osterix relative to day 0 levels. In addition, PEG-FG and PEG-LN gels were associated with increased deposition of bone ECM protein osteocalcin relative to PEG-FN gels and day 0. Importantly, the osteogenic response associated with FG and LN appeared to be specific in that markers for chondrocytic, smooth muscle cell, and adipocytic lineages were not similarly elevated relative to day 0 in these gels. To gain insight into the integrin dynamics underlying the observed differentiation results, initial integrin adhesion and temporal alterations in cell integrin profiles were evaluated. The associated results suggest that α2, αv, and α6 integrin subunits may play key roles in integrin-mediated osteogenesis.
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