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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)人子宫内膜样干细胞的分离与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了子宫内膜样干细胞。干细胞样细胞稳定增殖，甚至从一个单一的细胞没有雌激素超过2年。干细胞样细胞在形态和细胞生理上表现出异质性。(2)从子宫内膜异位症和子宫腺肌病组织中分离出干细胞，并对其进行鉴定。这些干细胞在形态上是同质的，提示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样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2年内停止了体外增殖，这与绝经后子宫内膜和腺肌组织的萎缩现象相吻合。(3)利用干细胞样细胞重塑子宫内膜组织：我们尝试通过腹腔注射分离的干细胞样细胞或子宫内膜组织碎片来重塑scid小鼠腹腔内的人子宫内膜组织。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任何子宫内膜组织在小鼠腹膜中生长。虽然几种细胞因子已被报道增加子宫内膜异位症患者的腹腔液中加入到矿注射子宫内膜细胞悬液，没有再生的子宫内膜组织中发现的小鼠。这些结果表明，正常子宫内膜异位组织来源于致癌性单克隆子宫内膜干细胞样细胞，子宫内膜异位组织不是简单的在位子宫内膜干细胞样细胞的植入。