Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine
Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine
复制标题
DOI：
10.1053/j.gastro.2005.03.085
复制
发表时间：
2005-06-01
期刊：
影响因子：
29.4
通讯作者：
Watanabe, M
中科院分区：
文献类型：
--
作者：
Matsumoto, T;Okamoto, R;Watanabe, M
背景与目的：我们已经报道了骨髓来源的细胞有助于人类肠道上皮细胞的再生。为了进一步分析这些细胞是如何产生、增殖和分化为上皮细胞的，使用内窥镜标本进行了组织学分析。方法：对14例性别不合的女性骨髓移植受者的30份活检标本进行检测。用Y染色体荧光原位杂交(FISH)和免疫组织化学方法鉴定骨髓来源细胞。用多色FISH排除细胞融合。进一步分析这些细胞的各种分化或增殖标记物。结果：未发现细胞融合的证据。骨髓来源的细胞不像干细胞那样分布在隐窝内，也很少表达Musashi-1。然而，骨髓来源的上皮细胞经常表达Ki-67，其中一些细胞呈成对的相邻细胞。这些细胞还表达所有4种终末分化细胞系的标记。在移植物抗宿主病后的再生过程中，Ki-67阳性细胞中的骨髓来源细胞数量显著增加。有趣的是，在骨髓来源的细胞中，表达分泌谱系细胞标志物的细胞数量显著增加。这种变化对于骨髓来源的细胞来说是独一无二的，导致骨髓来源的细胞在分泌系细胞中的比例显著增加。结论：骨髓来源的上皮细胞通过细胞融合以外的机制产生，很少产生干细胞。然而，这些细胞中有一小部分表达增殖标记，大多数作为终末分化细胞存在。在再生过程中，骨髓来源的细胞增加为分泌谱系细胞，从而有助于恢复上皮功能。
Background & Aims: We have previously reported that bone marrow (BM)-derived cells contribute to the regeneration of the human intestinal epithelium. To analyze further how these cells arise, proliferate, and differentiate as epithelial cells, histologic analysis was conducted using endoscopic specimens. Methods: Thirty biopsy specimens from 14 female, sex-mismatched BM-transplantation recipients were examined. BM-derived cells were identified by fluorescent in situ hybridization (FISH) for the Y chromosome and immunohistochemistry. Multicolor FISH was used to exclude cell fusion. These cells were further analyzed for various differentiation or proliferation markers. Results: No evidence of cell fusion was detected. BM-derived cells did not distribute within the crypt as stem cells and rarely expressed Musashi-1. However, BM-derived epithelial cells frequently expressed Ki-67, and some of these cells appeared as pairs of adjacent cells. These cells also expressed markers of all 4 lineages of terminally differentiated cells. During regeneration following graft-vs-host disease, the number of BM-derived cells was substantially increased within Ki-67-positive cells. Interestingly, the number of cells expressing markers for secretory lineage cells was significantly increased within BM-derived cells. This change was unique for BM-derived cells, resulting in a significantly increased proportion of BM-derived cells among secretory lineage cells. Conclusions: BM-derived epithelial cells arise via a mechanism other than cell fusion and rarely give rise to stem cells. However, a small proportion of these cells express proliferation markers, and a majority reside as terminally differentiated cells. During regeneration BM-derived cells increase as secretory lineage cells, thereby contributing to restore epithelial functions.