Label-retaining cells in the adult murine salivary glands possess characteristics of adult progenitor cells.
Label-retaining cells in the adult murine salivary glands possess characteristics of adult progenitor cells.
复制标题
DOI：
10.1371/journal.pone.0107893
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Limesand KH
中科院分区：
文献类型：
--
作者：
Chibly AM;Querin L;Harris Z;Limesand KH
放射治疗是头颈癌患者的主要治疗方法，全球每年约有50万例头颈癌患者。唾液腺功能障碍和相关的疾病，如口干症和吞咽困难，往往是由这些患者，大大降低了他们的生活质量。目前的预防和姑息治疗未能提供生活质量的改善，从而强调了对再生疗法的需求。在这项研究中，标记保留细胞（LRC）在小鼠唾液腺模型的开发，其中LRC表现出增殖潜力，并具有推定的唾液祖细胞的标记。出生后第10天用5-乙炔基-2 ′-脱氧尿苷（EdU）标记小鼠，并追踪8周。在追踪结束时获得的唾液腺组织切片显示LRC与唾液祖细胞标志物角蛋白5和角蛋白14以及kit mRNA之间的共定位，表明LRC包含唾液祖细胞的异质群体。通过球体测定证明LRC的增殖潜力，其中在初级和次级球体中发现LRC，并且它们在整个球体形成过程中与增殖标志物Ki 67共定位。令人惊讶的是，LRC被证明是放射抗性的，并且在放射处理后逃避细胞凋亡。这些研究结果的临床意义在于该模型的潜力，以研究防止唾液祖细胞在暴露于辐射后保持体内平衡的机制，这反过来将促进唾液腺功能障碍的再生疗法的发展。
Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction.
登录
查看更多内容
DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
2.7
作者：
Bullard, Tara;Koek, Laurie;Ovitt, Catherine E.
通讯作者：
Ovitt, Catherine E.
影响因子：
3.5
作者：
Castadot, Pierre;Lee, John A.;Gregoire, Vincent
通讯作者：
Gregoire, Vincent
DOI：
10.1002/ar.22746
发表时间：
2013-09-01
影响因子：
2
作者：
Gil-Perotin, Sara;Duran-Moreno, Maria;Manuel Garcia-Verdugo, Jose
通讯作者：
Manuel Garcia-Verdugo, Jose
DOI：
10.1016/j.ijrobp.2004.12.051
发表时间：
2005-07-15
影响因子：
7
作者：
Konings, AWT;Coppes, RP;Vissink, A
通讯作者：
Vissink, A