Isolation of human endometrial stem cells and remodeling of endometrial tissue

人子宫内膜干细胞的分离及子宫内膜组织的重塑

基本信息

批准号：
13671739
负责人：
UMESAKI Naohiko
金额：
$ 2.24万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671739/
关键词：
Endometrium Stem cell Endometrial stromal cell Endometriosis Adenomyosis

项目摘要

(1) Isolation and in vitro culture of human endometrial stem-like cellsWe have isolated the stem-like cells from several normal human endometrial tissues, with informed consents of patients. The stem-like cells stably proliferate even from a single cell without estrogen for more than 2 years. The stem-like cells showed morphologically and cytophysiologically heterogeneities.(2) Characterization of the stem-like cells derived from endometriotic and adenomyotic tissues.We have also isolated the stem-like cells from endometriotic and adenomyotic tissues. These stem-like cells were morphologically homogenous suggesting that endometriosis and adenomyosis tissues may be caused by monoclonal proliferation of atypical endometrial stem-like cells. The stem-like cells stopped the in vitro proliferation within 2 years without estrogen addition, which is coincided to postmenopausal atrophic phenomena of the endometriotic and adenomyotic tissues.(3) Remodeling of endometrial tissues with the stem-like cells.We tried to remodel of human endometrial tissues in scid mouse peritoneal cavity by intraperitoneal injection of isolated stem-like cells or small endometrial tissue fragments. Injection of small endometrial tissue fragments succeeded in remodeling endometrial tissue growths in mouse peritoneal surfaces. However, injection of endometrial cell suspensions did not make any endometrial tissue growth in mouse peritomneum. Although several cytokines which had been reported to increase in endometriotic patient peritoneal fluids were added to the mine injected with endometrial cell suspensions, no regenerated endometrial tissues were found in the mice. These results indicated that usual endometriotic tissues derived from oncogenic monoclonal endometrial stem-like cells and that endometriosis tissues were not simple implantation of eutopic endometrial stem-like cells.

(1)人子宫内膜干细胞的分离及体外培养我们在患者知情同意的情况下，从几种正常人子宫内膜组织中分离出干细胞。即使是在没有雌激素的情况下，干细胞样细胞在两年多的时间内也能稳定增殖。干细胞在形态学和细胞生理学上表现出异质性。(2)子宫内膜异位和子宫腺肌组织来源的干细胞的鉴定。我们还从子宫内膜异位和子宫腺肌组织中分离出了干细胞。这些干细胞样细胞在形态上是同质的，表明子宫内膜异位症和子宫腺肌病组织可能是由非典型子宫内膜干细胞的单克隆增殖引起的。在不添加雌激素的情况下，干细胞样细胞在体外2年内停止增殖，这与绝经后子宫内膜异位和子宫腺肌组织的萎缩现象相吻合。（3）干细胞样细胞对子宫内膜组织的重塑。通过腹腔注射分离的干细胞样细胞或小的子宫内膜组织碎片，将人子宫内膜组织置于 scid 小鼠腹膜腔中。注射小的子宫内膜组织碎片成功地重塑了小鼠腹膜表面的子宫内膜组织生长。然而，注射子宫内膜细胞悬液并没有使小鼠腹膜内出现任何子宫内膜组织生长。尽管在注射子宫内膜细胞悬液的矿井中添加了几种据报道会在子宫内膜异位症患者腹腔液中增加的细胞因子，但在小鼠体内没有发现再生的子宫内膜组织。这些结果表明，通常的子宫内膜异位组织来源于致癌单克隆子宫内膜干细胞，并且子宫内膜异位组织不是在位子宫内膜干细胞的简单植入。