Selective functionalization of nanofiber scaffolds to regulate salivary gland epithelial cell proliferation and polarity.
Selective functionalization of nanofiber scaffolds to regulate salivary gland epithelial cell proliferation and polarity.
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DOI：
10.1016/j.biomaterials.2012.08.021
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发表时间：
2012-11
期刊：
影响因子：
14
通讯作者：
Larsen, Melinda
中科院分区：
文献类型：
--
作者：
Cantara, Shraddha I.;Soscia, David A.;Sequeira, Sharon J.;Jean-Gilles, Riffard P.;Castracane, James;Larsen, Melinda
当在2D基质上培养时，上皮细胞类型通常会失去顶基极性，但分泌细胞(如唾液腺腺泡细胞)的定向分泌需要顶基极性。我们在模拟基底膜的聚乳酸-乙醇酸共聚(PLGA)纳米纤维支架上培养唾液腺上皮细胞，并检测细胞增殖和根尖细胞极化。虽然细胞在纳米纤维上增殖，但壳聚糖包覆的纳米纤维支架刺激了唾液腺上皮细胞的增殖。尽管根据ZO-1的顶端定位，纳米纤维支架相对于平坦表面促进了根尖基底细胞的极性，但壳聚糖的存在对其有拮抗作用。无论是唾液腺腺泡还是导管细胞，都不能在纳米纤维支架上完全极化，这是由成熟的紧密连接标记occludin的均匀膜分布决定的。然而，根据封闭素的顶端定位，使用基底膜蛋白Layinin-111进行化学功能化的纳米纤维支架促进了更成熟的紧密连接，但不影响细胞增殖。为了模拟基底膜的多功能功能，制备了双功能PLGA纳米纤维。腺泡细胞和导管细胞系都对壳聚糖和层粘连蛋白-111偶联的双功能支架提供的信号产生反应，证明了这种支架对上皮细胞类型的适用性。
Epithelial cell types typically lose apicobasal polarity when cultured on 2D substrates, but apicobasal polarity is required for directional secretion by secretory cells, such as salivary gland acinar cells. We cultured salivary gland epithelial cells on poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds that mimic the basement membrane, a specialized extracellular matrix, and examined cell proliferation and apicobasal polarization. Although cells proliferated on nanofibers, chitosan-coated nanofiber scaffolds stimulated proliferation of salivary gland epithelial cells. Although apicobasal cell polarity was promoted by the nanofiber scaffolds relative to flat surfaces, as determined by the apical localization of ZO-1, it was antagonized by the presence of chitosan. Neither salivary gland acinar nor ductal cells fully polarized on the nanofiber scaffolds, as determined by the homogenous membrane distribution of the mature tight junction marker, occludin. However, nanofiber scaffolds chemically functionalized with the basement membrane protein, laminin-111, promoted more mature tight junctions, as determined by apical localization of occludin but did not affect cell proliferation. To emulate the multifunctional capabilities of the basement membrane, bifunctional PLGA nanofibers were generated. Both acinar and ductal cell lines responded to signals provided by bifunctional scaffolds coupled to chitosan and laminin-111, demonstrating the applicability of such scaffolds for epithelial cell types.
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