Development of a functional salivary gland tissue chip with potential for high-content drug screening.
Development of a functional salivary gland tissue chip with potential for high-content drug screening.
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DOI：
10.1038/s42003-021-01876-x
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发表时间：
2021-03-19
影响因子：
5.9
通讯作者：
Benoit DSW
中科院分区：
文献类型：
--
作者：
Song Y;Uchida H;Sharipol A;Piraino L;Mereness JA;Ingalls MH;Rebhahn J;Newlands SD;DeLouise LA;Ovitt CE;Benoit DSW
头颈癌的放射治疗会导致唾液腺功能障碍，导致永久性口干症。新治疗策略的发现进展有限，原因是缺乏模拟唾液腺功能并允许高通量药物筛选的体外模型。我们通过将工程细胞外基质与微泡（MB）阵列技术相结合来开发小鼠和人类唾液腺的功能组织模拟物来解决这一限制。我们证明，封装在 MB 阵列中形成的基质金属蛋白酶可降解的聚乙二醇水凝胶内的小鼠和人类唾液组织是可行的，表达关键的唾液腺标记物，并表现出功能蛋白的极化定位。唾液腺模拟物（SGm）响应钙信号激动剂并分泌唾液蛋白。然后使用 SGm 来评估辐射敏感性和使用辐射防护化合物减轻辐射损伤的情况。总而言之，SGm 显示了唾液腺的表型和功能参数，并为高内涵/通量药物测试提供了支持技术。宋、内田和沙里波尔等人。通过将工程细胞外基质与微泡阵列技术相结合，开发小鼠和人类唾液腺的功能组织模拟物。由此产生的组织模拟物模拟唾液腺的表型和功能，并为高内涵/通量药物测试提供了希望。
Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing. Song, Uchida, and Sharipol et al. develop functional tissue mimetics for mouse and human salivary glands by combining engineered extracellular matrices with microbubble array technology. The resulting tissue mimetics emulate phenotype and function of salivary glands and provide promise for high-content/throughput drug testing.
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在药物发现的边界，片上的器官。
DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Esch EW;Bahinski A;Huh D
通讯作者：
Huh D
影响因子：
4.8
作者：
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DOI：
10.1016/j.jconrel.2014.05.004
发表时间：
2014-09-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Bhise NS;Ribas J;Manoharan V;Zhang YS;Polini A;Massa S;Dokmeci MR;Khademhosseini A
通讯作者：
Khademhosseini A
影响因子：
46.9
作者：
Bhatia, Sangeeta N.;Ingber, Donald E.
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Ingber, Donald E.
影响因子：
14
作者：
Adine, Christabella;Ng, Kiaw K.;Ferreira, Joao N.
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Ferreira, Joao N.