Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells
Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells
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DOI：
10.1073/pnas.0704472104
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发表时间：
2007-11-20
影响因子：
11.1
通讯作者：
Matsuzaki, Yumi
中科院分区：
文献类型：
--
作者：
Ono, Masanori;Maruyama, Tetsuo;Matsuzaki, Yumi
在怀孕期间，人类子宫的体积增加了500到1000倍，重量增加了24倍。子宫平滑肌层或肌层重塑，细胞肥大和增生明显。然而，新的平滑肌细胞的来源尚不清楚。它们可能起源于现有的平滑肌细胞，也可能是干细胞分化的产物。这项研究描述了从未怀孕的人子宫肌层分离出来的肌层细胞的一个子集，它代表了子宫肌层干细胞群体。这是一个明显的Hoechst染料外流模式的子宫肌层细胞侧群(MyoSP)。与主要的肌层细胞(MyoMP)不同，myoSP停留在静止状态，低表达或缺乏肌层细胞标志物，只有在低氧浓度下才能在体外增殖并最终分化为成熟的肌层细胞。虽然myoMP在体外培养前后显示出成熟的肌层表型，但当移植到严重免疫缺陷小鼠的子宫中时，只有myoSP而不是myoMP能有效地产生有功能的人子宫肌层组织。最后，在适宜的诱导分化条件下，myoSP具有多向分化潜能，并在体外向成骨细胞和脂肪细胞分化。因此，myoSP具有子宫肌层干细胞的表型和功能特征。对myoSP的研究将有助于加深对子宫肌层生理学和肌层衍生疾病(如肌瘤)发病机制的了解。MyoSP也可能是一种新的生物材料来源，不仅可以用于重建人类的子宫，还可以用于重建其他器官。
Over the course of pregnancy, the human uterus undergoes a 500- to 1,000-fold increase in volume and a 24-fold increase in weight. The uterine smooth muscle layer or myometrium is remodeled, and both cell hypertrophy and hyperplasia are evident. The origin of the new smooth muscle cells, however, is unclear. They may arise from existing smooth muscle cells, or they may be the product of stem cell differentiation. This study describes a subset of myometrial cells isolated from nonpregnant human myometrium that represents the myometrial stem cell population. This was characterized as side population of myometrial cells (myoSP) by a distinct Hoechst dye efflux pattern. In contrast to the main population of myometrial cells (myoMP), myoSP resided in quiescence, underexpressed or lacked myometrial cell markers, and could proliferate and eventually differentiate into mature myometrial cells in vitro only under low oxygen concentration. Although myoMP displayed mature myometrial phenotypes before and after in vitro cultivation, only myoSP, not myoMP, generated functional human myometrial tissues efficiently when transplanted into the uteri of severely immunodeficient mice. Finally, myoSP were multi-potent and made to differentiate into osteocytes and adipocytes in vitro under the appropriate differentiation-inducing conditions. Thus, myoSP exhibited phenotypic and functional characteristics of myometrial stem cells. Study of myoSP will improve the understanding of myometrial physiology and the pathogenesis of myometrium-derived diseases such as leiomyoma. myoSP may also represent a novel source of biological material that could be used in the reconstruction of not only the human uterus but also other organs as well.