Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus
Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus
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DOI：
10.1053/j.gastro.2012.12.022
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发表时间：
2013-04-01
期刊：
影响因子：
29.4
通讯作者：
Jankowski, Janusz A.
中科院分区：
文献类型：
--
作者：
Pan, Qiuwei;Nicholson, Anna M.;Jankowski, Janusz A.
背景与目的：缓慢循环的成体干细胞的存在受到了活跃循环细胞的鉴定的挑战。我们通过追踪5-碘-2 '-脱氧尿苷（IdU）标记保留细胞（LRC），研究了正常食管、Barrett食管（BE）、食管异型增生、腺癌和患者健康胃组织中未定型、缓慢循环细胞的存在。方法：4例患者（3例接受食管切除术，1例接受食管内镜粘膜切除术治疗异型增生，1例接受食管腺癌食管切除术）在30分钟内静脉输注IdU（200 mg/m2体表面积;最大剂量400 mg）; IdU的循环半衰期为8小时。在输注后7、11、29和67天，从健康食管、BE、异型增生、腺癌和健康胃区域收集组织;通过原位杂交、流式细胞术和免疫组织化学分析进行分析。研究结果：在发育不良或腺癌中未发现LRC，但在BE组织的腺体基部、食管鳞状上皮基底层的乳头和健康胃的颈部/峡部区域中存在大量LRC。这些细胞循环缓慢，因为IdU保留至少67天，并且与Ki-67的共标记不常见。在BE组织的腺体中，大多数细胞不表达防御素-5，Muc-2或嗜铬粒蛋白A，表明它们不是谱系定型的。一些细胞在67天时标记有内分泌标记物和IdU;这些细胞代表了一个小群体（
BACKGROUND & AIMS: The existence of slowly cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients. METHODS: Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg/m(2) body surface area; maximum dose, 400 mg) over a 30-minute period; the IdU had a circulation half-life of 8 hours. Tissues were collected at 7, 11, 29, and 67 days after infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses. RESULTS: No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (