Orciani Monia, Caffarini Miriam, Biagini Alessandra, Lucarini Guendalina, Delli Carpini Giovanni, Berretta Antonella, Di Primio Roberto, Ciavattini Andrea
Department of Clinical and Molecular Sciences and Histology, Università Politecnica delle Marche, 60126 Ancona, Italy.
Department of Clinical Science, Università Politecnica delle Marche, 60126 Ancona, Italy.
Stem Cells Int. 2018 May 13;2018:1716246. doi: 10.1155/2018/1716246. eCollection 2018.
Although the etiology of leiomyoma is unclear, a progenitor/undifferentiated cell population has been described whose dysregulation may be involved in the onset of uterine conditions. Moreover, inflammation is involved in the development of several tumors. The aim of this work was to understand if progenitor cells sustain a chronic inflammatory microenvironment that enhances leiomyoma development. Cells from 12 human leiomyoma and 12 normal myometrium samples of the same patients were in vitro isolated and exhaustively characterized (morphology, proliferation, cytofluorometry, differentiation, RT-PCR, immunofluorescence, immunohistochemistry, and Western blotting assays). Selected cytokines (ELISA) and inflammation-related genes (RT-PCR) were analyzed to identify healthy myometrium progenitor cells (MPCs) and leiomyoma progenitor cells (LPCs). Results show that (i) MPCs and LPCs share stemness features, such as immunophenotype and multidifferentiation assay, (ii) LPCs have a significantly shorter doubling time and a significantly higher expression of stemness genes ( < 0.05), and (iii) LPCs secreted significantly higher levels ( < 0.05) of cytokines related to chronic inflammation and significantly lower amounts ( < 0.05) of cytokines related to acute inflammation. Despite the limited sample size, comparisons between leiomyoma and normal myometrium tissue from each patient allowed normalization of patient-specific differences. The evidenced cytokine expression pattern related to chronic inflammation in LPCs may play a role in the increased risk of adverse obstetric outcomes (infertility, spontaneous miscarriage, and preterm birth) in women affected by leiomyomas. These women should be recognized as "high risk" and subjected to specialized management both before and during pregnancy.
尽管平滑肌瘤的病因尚不清楚，但已描述了一种祖细胞/未分化细胞群，其失调可能与子宫疾病的发生有关。此外，炎症与多种肿瘤的发展有关。这项工作的目的是了解祖细胞是否维持一种促进平滑肌瘤发展的慢性炎症微环境。从12例平滑肌瘤患者和12例同一患者的正常子宫肌层样本中体外分离细胞，并进行全面表征（形态学、增殖、细胞荧光分析、分化、逆转录-聚合酶链反应、免疫荧光、免疫组织化学和蛋白质印迹分析）。分析选定的细胞因子（酶联免疫吸附测定）和炎症相关基因（逆转录-聚合酶链反应），以鉴定健康子宫肌层祖细胞（MPCs）和平滑肌瘤祖细胞（LPCs）。结果表明：（i）MPCs和LPCs具有共同的干性特征，如免疫表型和多分化分析；（ii）LPCs的倍增时间显著缩短，干性基因表达显著升高（<0.05）；（iii）LPCs分泌的与慢性炎症相关的细胞因子水平显著更高（<0.05），而与急性炎症相关的细胞因子水平显著更低（<0.05）。尽管样本量有限，但对每位患者的平滑肌瘤组织和正常子宫肌层组织进行比较，可使患者特异性差异标准化。LPCs中与慢性炎症相关的细胞因子表达模式的证据可能在受平滑肌瘤影响的女性不良产科结局（不孕、自然流产和早产）风险增加中起作用。这些女性应被视为“高危”人群，并在怀孕前和怀孕期间接受专门管理。
