Polysaccharide-Based Polyelectrolyte Multi layer Surface Coatings can Enhance Mesenchymal Stem Cell Response to Adsorbed Growth Factors

Polysaccharide-Based Polyelectrolyte Multi layer Surface Coatings can Enhance Mesenchymal Stem Cell Response to Adsorbed Growth Factors
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DOI:
10.1021/bm1005799
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发表时间:
2010-10-01
期刊:
影响因子:
6.2
通讯作者:
Kipper, Matt. J.
Kipper, Matt. J.
中科院分区:
化学2区
文献类型:
--
作者:
Almodovar, Jorge;Bacon, Samantha;Kipper, Matt. J.

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人们普遍认为,表面化学和生化信号都会影响间充质干细胞 (MSC) 的增殖和分化。对 MSC 行为有强烈影响的几种生长因子与糖胺聚糖相互作用,从而影响其稳定性和生化活性。这项工作的目标是开发基于多糖的聚电解质多层 (PEM) 来结合和稳定生长因子,以输送至 MSC。使用天然衍生的多糖壳聚糖和肝素,在镀金玻璃芯片、组织培养聚苯乙烯 (TCPS) 和钛上构建 PEM。通过傅里叶变换表面等离子共振评估 PEM 的构建和碱性成纤维细胞生长因子 (FGF-2) 对 PEM 的吸附。 X射线光电子能谱、偏振调制红外反射吸收光谱。功能性的。在存在或不存在吸附的纤连蛋白的情况下,体外评估了骨髓来源的绵羊 MSC 对 PEM 包被的 TCPS 和钛上的 FGF-2 的反应。使用低血清培养基评估 FGF-2 剂量和呈递对 MSC 附着和增殖的影响,历时四天。在 PEM 包被的 TCPS 上,我们发现,与任何其他测试条件(包括以最佳促有丝分裂剂量在溶液中递送 FGF-2)相比,吸附到具有吸附纤连蛋白的肝素封端 PEM 上的 FGF-2 诱导更大的细胞密度和更高的增殖率或 MSC。当 FGF-2 通过吸附到 PEM 上递送时,第四天的细胞密度比 FGF-2 在溶液中递送时高 1.8 倍。该系统代表了表面涂层开发的一个有前途的候选者,可以稳定和增强治疗应用中生长因子的活性。有趣的是,当 FGF-2 通过吸附到钛上的 PEM 上时,没有观察到相同的效果。当在钛上形成基于多糖的PEM时,绵羊MSC对吸附的FGF-2的增殖反应不如对溶液中递送的FGF-2的反应强烈。
It is generally accepted that both surface chemistry and biochemical cues affect mesenchymal stem cell (MSC) proliferation and differentiation, Several growth factors that have strong influences on MSC behavior bind to glycosaminoglycans in interactions that affect their stability and their biochemical activity. The goal of this work was to develop polysaccharide-based polyelectrolyte multilayers (PEMs) to bind and stabilize growth factors for delivery to MSCs. Using the naturally derived polysaccharides chitosan and heparin, PEMs were constructed on gold-coated glass chips, tissue-culture polystyrene (TCPS), and titanium. PEM construction and basic fibroblast growth factor (FGF-2) adsorption to PEMs were evaluated by Fourier transform surface plasmon resonance. X-ray photoelectron spectroscopy, and polarization modulation infrared reflection absorption spectroscopy. The functional. response of bone marrow-derived ovine MSCs to FGF-2 on PEM-coated TCPS and titanium was evaluated in vitro, in the presence and absence of adsorbed fibronectin. The effect of FGF-2 dose and presentation on MSC attachment and proliferation was evaluated using low-serum Media, over four days. On PEM-coated TCPS, we found that FGF-2 adsorbed to heparin-terminated PEMs with adsorbed fibronectin induces greater cell density and a higher proliferation rate or MSCs than any of the other conditions tested, including delivery of the FGF-2 in solution, at an optimally mitogenic dose. Cell densities on day four were 1.8 times higher when FGF-2 was delivered by adsorption to the PEM than when FGF-2 was delivered in solution. This system represents a promising candidate far the development of surface coatings that can Stabilize and potentiate the activity of growth factors for therapeutic applications. Interestingly, the same effects were not observed when FGF-2 was delivered by adsorption to PEMs on titanium. When the polysaccharide-based PEMs were formed on titanium, the proliferative response or ovine MSCs to adsorbed FGF-2 was not :is strong as the response to FGF-2 delivered in solution.