ROCK inhibitor increases proacinar cells in adult salivary gland organoids
ROCK inhibitor increases proacinar cells in adult salivary gland organoids
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DOI：
10.1016/j.scr.2019.101608
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发表时间：
2019-12-01
影响因子：
1.2
通讯作者：
Larsen, Melinda
中科院分区：
文献类型：
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作者：
Koslow, Matthew;O'Keefe, Kevin J.;Larsen, Melinda
来自萨尔球的成人上皮细胞已经被用来改善受辐射的小鼠唾液腺的唾液产生。重要的是，优化碱蓬的细胞组成可以提高它们的再生能力。Rho Kinase(ROCK)抑制剂Y27632已被用于促进体外培养的祖细胞的增殖和减少凋亡。在这项研究中，我们研究了Y27632是否可用于促进成人颌下腺上皮祖细胞的扩增，或在不同的培养条件下影响其分化潜能。Y27632可促进Kit(+)和Mist1(+)细胞的增殖，而在单纯含血清的培养液中，Y27632可增加表达K5基本祖细胞标志物的细胞数量。从Mist1(CreERT2)和R26(TdTomato)小鼠衍生的Salisphere在Y27632培养的Salisphere中包括Mist1来源的细胞。当这些丹参被结合到3D器官中时，在柳叶阶段包含Y27632增加了表达腺泡/腺泡标志水通道蛋白5(AQP5)的Mist1来源细胞对FGF2依赖的间充质信号的响应。优化丹参和类有机物的细胞组成可用于改善成人唾液祖细胞在再生医学策略中的应用。
Salisphere-derived adult epithelial cells have been used to improve saliva production of irradiated mouse salivary glands. Importantly, optimization of the cellular composition of salispheres could improve their regenerative capabilities. The Rho Kinase (ROCK) inhibitor, Y27632, has been used to increase the proliferation and reduce apoptosis of progenitor cells grown in vitro. In this study, we investigated whether Y27632 could be used to improve expansion of adult submandibular salivary epithelial progenitor cells or to affect their differentiation potential in different media contexts. Application of Y27632 in medium used previously to grow salispheres promoted expansion of Kit(+) and Mist1(+) cells, while in simple serum-containing medium Y27632 increased the number of cells that expressed the K5 basal progenitor marker. Salispheres derived from Mist1(CreERT2); R26(TdTomato) mice grown in salisphere media with Y27632 included Mistl-derived cells. When these salispheres were incorporated into 3D organoids, inclusion of Y27632 in the salisphere stage increased the contribution of Mist1-derived cells expressing the proacinar/acinar marker, Aquaporin 5 (AQP5), in response to FGF2-dependent mesenchymal signals. Optimization of the cellular composition of salispheres and organoids can be used to improve the application of adult salivary progenitor cells in regenerative medicine strategies.