Chronic Inflammation May Enhance Leiomyoma Development by the Involvement of Progenitor Cells

Abstract

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 (p < 0.05), and (iii) LPCs secreted significantly higher levels (p < 0.05) of cytokines related to chronic inflammation and significantly lower amounts (p < 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.

How the Pathological Microenvironment Affects the Behavior of Mesenchymal Stem Cells in the Idiopathic Pulmonary Fibrosis

“…Since it has been demonstrated that MSCs from pathological tissues acquire specific features [21], the expression of the main molecules characterizing IPF was analyzed in IPF-MSCs and C-MSCs.…”

“…The expression of α-SMA, collagen type 1 (COL1A1), fibronectin, and TGF-β1 was faint in C-MSCs whereas IPF-MSCs showed a strong expression ( Figure 3). The percentage of cells area occupied by the proteins, calculated using Fiji-ImageJ software (available online at https://imagej.net/Fiji) [22], in IPF-MSCs was significantly higher than C-MSC (Table 1) Since it has been demonstrated that MSCs from pathological tissues acquire specific features [21], the expression of the main molecules characterizing IPF was analyzed in IPF-MSCs and C-MSCs. The expression of α-SMA, collagen type 1 (COL1A1), fibronectin, and TGF-β1 was faint in C-MSCs whereas IPF-MSCs showed a strong expression ( Figure 3A).…”

“…MSCs isolated from patients affected by idiopathic pulmonary fibrosis were named IPF-MSCs, while MSCs isolated from control lung of patients with adenocarcinoma were defined C-MSCs. According to the criteria by Dominici [20], cells were characterized by testing the plastic adherence, the immunophenotype and the multipotency as previously described [21,44]. Finally, the expression of genes related to stemness (OCT4, SOX2, NANOG, KFL4) was analyzed by qRT-PCR.…”

Contemporary concepts of uterine fibroids’ pathogenesis

“…Таким образом, развитие миомы может быть результатом нарушения функции, пролиферации и дифференцировки недифференцированных клеток миометрия, которые находятся под действием гормонов яичников. Авторы также указывают на возможное влияние воспалительного процесса на дисрегуляцию клеток-предшественников [21].…”

The Emerging Spectrum of Early Life Exposure-Related Inflammation and Epigenetic Therapy

“…In addition, the levels of tumor necrosis factor TNF-α, a cell-signaling protein involved in systemic inflammation, is elevated in Caucasian women with clinically symptomatic UFs [53]. A recent study also shows that UF progenitor cells secrete higher levels of Th2 pathway cytokines (IL4, IL-5, IL-10, and IL-13), and significantly lower levels of Th1/Th17 cytokines (IL-6, IL-12, IL-17A, INF-γ, G-CSF, and TGF-β1), suggesting that the altered pattern of cytokine expression and secretion may enhance UF development via chronic inflammation with the involvement of infiltrating immune cells [54]. …”