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Selective functionalization of nanofiber scaffolds to regulate salivary gland epithelial cell proliferation and polarity

机译:纳米纤维支架的选择性功能化,以调节唾液腺上皮细胞的增殖和极性

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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.
机译:当在2D基质上培养时,上皮细胞类型通常会失去顶点突触极性,但是对于分泌细胞(如唾液腺腺泡细胞)的定向分泌来说,顶点突触极性是必需的。我们在聚乳酸-乙醇酸(PLGA)纳米纤维支架上培养唾液腺上皮细胞,该支架模仿基底膜,一种专门的细胞外基质,并检查了细胞增殖和apapobasal极化。尽管细胞在纳米纤维上增殖,但是壳聚糖包被的纳米纤维支架刺激唾液腺上皮细胞的增殖。尽管通过ZO-1的根尖定位确定,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,但由于壳聚糖的存在,它被拮抗了。唾液腺腺泡或导管细胞在纳米纤维支架上均未完全极化,这由成熟的紧密连接标记物occludin的均质膜分布确定。然而,由基底膜蛋白层粘连蛋白-111化学功能化的纳米纤维支架可促进更成熟的紧密连接,这是由occludin的根尖定位确定的,但不影响细胞增殖。为了模拟基膜的多功能功能,生成了双功能PLGA纳米纤维。腺泡和导管细胞系均响应由与壳聚糖和层粘连蛋白-111偶联的双功能支架提供的信号,证明了此类支架对上皮细胞类型的适用性。

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