CD34 and CD49f Double-Positive and Lineage Marker-Negative Cells Isolated from Human Myometrium Exhibit Stem Cell-Like Properties Involved in Pregnancy-Induced Uterine Remodeling.
CD34 and CD49f Double-Positive and Lineage Marker-Negative Cells Isolated from Human Myometrium Exhibit Stem Cell-Like Properties Involved in Pregnancy-Induced Uterine Remodeling.
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DOI：
10.1095/biolreprod.114.127126
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发表时间：
2015-08
影响因子：
3.6
通讯作者：
Maruyama T
中科院分区：
文献类型：
--
作者：
Ono M;Kajitani T;Uchida H;Arase T;Oda H;Uchida S;Ota K;Nagashima T;Masuda H;Miyazaki K;Asada H;Hida N;Mabuchi Y;Morikawa S;Ito M;Bulun SE;Okano H;Matsuzaki Y;Yoshimura Y;Maruyama T
反复和戏剧性的妊娠引起的子宫增大和重塑整个生殖生命表明子宫平滑肌干/祖细胞的存在。本研究的目的是分离和鉴定干/祖细胞样细胞从人子宫肌层通过特定的表面标记。我们在此鉴定了CD 49 f和CD 34作为标记物，以允许从人子宫肌层中选择干/祖细胞样群体，并表明人CD 45-CD 31-血型糖蛋白A-和CD 49 f + CD 34+子宫肌层细胞表现出干细胞样特性。这些包括侧群表型、未分化状态、高集落形成能力、向平滑肌细胞、成骨细胞、脂肪细胞和软骨细胞的多谱系分化以及异种移植后的体内子宫肌层组织重建。此外，CD 45-CD 31-血型糖蛋白A-和CD 49 f + CD 34+子宫肌层细胞在体外缺氧条件下增殖，与未处理的非妊娠子宫肌层相比，在雌激素处理的非妊娠子宫肌层中显示出更大的扩增，并且在异种移植后小鼠的妊娠子宫肌层中进一步显示出更大的扩增。这些结果表明，新发现的子宫肌层干/祖细胞样细胞缺氧和性类固醇的影响可能参与妊娠诱导的子宫增大和重塑，提供新的见解人类子宫肌层生理。
Repeated and dramatic pregnancy-induced uterine enlargement and remodeling throughout reproductive life suggests the existence of uterine smooth muscle stem/progenitor cells. The aim of this study was to isolate and characterize stem/progenitor-like cells from human myometrium through identification of specific surface markers. We here identify CD49f and CD34 as markers to permit selection of the stem/progenitor cell-like population from human myometrium and show that human CD45– CD31– glycophorin A– and CD49f+ CD34+ myometrial cells exhibit stem cell-like properties. These include side population phenotypes, an undifferentiated status, high colony-forming ability, multilineage differentiation into smooth muscle cells, osteoblasts, adipocytes, and chondrocytes, and in vivo myometrial tissue reconstitution following xenotransplantation. Furthermore, CD45– CD31– glycophorin A– and CD49f+ CD34+ myometrial cells proliferate under hypoxic conditions in vitro and, compared with the untreated nonpregnant myometrium, show greater expansion in the estrogen-treated nonpregnant myometrium and further in the pregnant myometrium in mice upon xenotransplantation. These results suggest that the newly identified myometrial stem/progenitor-like cells influenced by hypoxia and sex steroids may participate in pregnancy-induced uterine enlargement and remodeling, providing novel insights into human myometrial physiology.