BACKGROUND In Asherman's syndrome (AS), intrauterine scarring and fibrotic adhesions lead to menstrual disorders, pregnancy loss, or infertility. A few clinical trials have piloted cell therapy to overcome AS. Understanding the role of the stromal compartment in endometrial regeneration remains poorly understood. We hypothesize that endometrial stromal cells (eSCs) represent a relevant cell population to establish novel cell-based therapeutics for endometrial disorders. The aim of this study was to characterize eSCs and evaluate their immune-cell interactions. METHODS eSCs were isolated from healthy donors, during the proliferative stage of the menstrual cycle. Cells were characterized for expression of mesenchymal stromal cell (MSC) markers and assessed for their tumorigenic potential. eSCs were co-cultured with interferon γ and tumor necrosis factor α, and cell surface expression of their respective receptors and human leukocyte antigen (HLA) I and II determined by flow cytometry. Secreted levels of key immunomodulatory factors were established. eSCs were cultured with activated peripheral blood mononuclear cells, and T cell differentiation and proliferation determined. RESULTS eSCs demonstrated an MSC surface phenotype and exhibited multipotency. Expanded eSCs retained chromosomal stability and demonstrated no tumorigenicity. Upon stimulation, eSCs licensed to an anti-inflammatory phenotype with upregulated secretion of immunomodulatory factors. Stimulated eSCs did not express HLA class II. eSCs suppressed the proliferation and activation of CD4+ T cells, with the eSC secretome further downregulating central memory T cells and upregulating effector memory (EM) cells. CONCLUSIONS Differential responsiveness to inflammation by eSCs, compared to other MSC sources, demonstrates the need to understand the specific functional effects of individual stromal cell sources. A lack of HLA class II and triggering of EM T cell differentiation strongly links to innate in vivo roles of eSCs in tissue repair and immune tolerance during pregnancy. We conclude that eSCs may be an ideal cell therapy candidate for endometrial disorders.

中文翻译：

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子宫内膜间质细胞表现出独特的表型和免疫调节特性。

背景技术在阿舍曼综合症（AS）中，子宫内瘢痕形成和纤维化粘连导致月经失调，妊娠减少或不育。一些临床试验已经尝试了细胞疗法来克服AS。了解间质隔在子宫内膜再生中的作用仍然知之甚少。我们假设子宫内膜间质细胞（eSCs）代表相关的细胞群体，以建立新型的基于细胞的子宫内膜疾病治疗剂。这项研究的目的是表征eSCs并评估其免疫细胞相互作用。方法在月经周期的增殖期，从健康供体中分离出eSC。表征细胞的间充质基质细胞（MSC）标记的表达，并评估其致瘤潜力。将eSC与干扰素γ和肿瘤坏死因子α共培养，并通过流式细胞术确定其各自受体和人类白细胞抗原（HLA）I和II的细胞表面表达。确定了关键免疫调节因子的分泌水平。用激活的外周血单个核细胞培养eSC，并确定T细胞的分化和增殖。结果eSCs表现出MSC表面表型并表现出多能性。扩展的eSCs保留了染色体稳定性，并没有显示致瘤性。刺激后，eSC许可具有抗炎表型，且免疫调节因子的分泌上调。受刺激的eSC不表达HLA II类。eSCs抑制CD4 + T细胞的增殖和活化，与eSC分泌组一起进一步下调中央记忆T细胞并上调效应记忆（EM）细胞。结论与其他MSC来源相比，eSC对炎症反应的差异性表明需要了解单个基质细胞来源的特定功能作用。缺乏HLA II类和触发EM T细胞分化与妊娠期eSC在组织修复和免疫耐受中的先天体内作用密切相关。我们得出的结论是，eSCs可能是子宫内膜疾病的理想细胞疗法候选人。缺乏HLA II类和触发EM T细胞分化与妊娠期eSC在组织修复和免疫耐受中的先天体内作用密切相关。我们得出的结论是，eSCs可能是子宫内膜疾病的理想细胞疗法候选人。缺乏HLA II类和触发EM T细胞分化与妊娠期eSC在组织修复和免疫耐受中的先天体内作用密切相关。我们得出的结论是，eSCs可能是子宫内膜疾病的理想细胞疗法候选人。