Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics.
Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics.
复制标题
DOI：
10.1016/j.actbio.2016.12.049
复制
发表时间：
2017-03-01
影响因子：
9.7
通讯作者：
Benoit DSW
中科院分区：
文献类型：
--
作者：
Shubin AD;Felong TJ;Schutrum BE;Joe DSL;Ovitt CE;Benoit DSW
头颈部癌症的放射治疗由于唾液腺中分泌腺泡细胞的损失而导致永久性口干症。利用原代下颌下腺（SMG）细胞的再生治疗显示出唾液分泌功能的适度改善，但唾液腺再生的证据有限。我们最近已经表明，聚（乙二醇）（PEG）水凝胶可以支持SMG细胞的生存和增殖作为多细胞球体在体外。为了进一步开发这种基于细胞的唾液腺再生方法，我们研究了PEG水凝胶降解的不同模式如何影响包封的唾液腺球体内的增殖、细胞特异性基因表达和上皮形态。不可降解的，水解降解的，基质金属蛋白酶（MMP）可降解的，和混合模式可降解的水凝胶的比较表明，水凝胶降解的任何机制所需的显着增殖的包囊细胞。与其他水凝胶组合物相比，腺泡表型标记物Aqp 5和Nkcc 1的表达在MMP可降解的水凝胶中增加。然而，分泌型腺泡蛋白Mist 1和Pip的表达没有维持在与表型标记相同的程度，这表明封装后细胞功能的变化。然而，MMP-和混合模式的降解性促进组织的极化细胞类型形成紧密连接和表达的基底膜蛋白层粘连蛋白和胶原蛋白IV封装SMG球体内。这项工作表明，细胞重塑的水凝胶可以促进增殖和腺样组织封装的唾液腺细胞，以及再生方法所需的腺泡细胞特性的维护。需要研究以确定进一步增强腺泡分泌特性的方法。
Radiation therapy for head and neck cancers leads to permanent xerostomia due to the loss of secretory acinar cells in the salivary glands. Regenerative treatments utilizing primary submandibular gland (SMG) cells show modest improvements in salivary secretory function, but there is limited evidence of salivary gland regeneration. We have recently shown that poly(ethylene glycol) (PEG) hydrogels can support the survival and proliferation of SMG cells as multicellular spheres in vitro. To further develop this approach for cell-based salivary gland regeneration, we have investigated how different modes of PEG hydrogel degradation affect the proliferation, cell-specific gene expression, and epithelial morphology within encapsulated salivary gland spheres. Comparison of non-degradable, hydrolytically-degradable, matrix metalloproteinase (MMP)-degradable, and mixed mode-degradable hydrogels showed that hydrogel degradation by any mechanism is required for significant proliferation of encapsulated cells. The expression of acinar phenotypic markers Aqp5 and Nkcc1 was increased in hydrogels that are MMP-degradable compared with other hydrogel compositions. However, expression of secretory acinar proteins Mist1 and Pip was not maintained to the same extent as phenotypic markers, suggesting changes in cell function upon encapsulation. Nevertheless, MMP- and mixed mode-degradability promoted organization of polarized cell types forming tight junctions and expression of the basement membrane proteins laminin and collagen IV within encapsulated SMG spheres. This work demonstrates that cellularly remodeled hydrogels can promote proliferation and gland-like organization by encapsulated salivary gland cells as well as maintenance of acinar cell characteristics required for regenerative approaches. Investigation is required to identify approaches to further enhance acinar secretory properties.