文章：

多发性骨髓瘤中的炎性骨髓间充质干细胞：转录特征与体外建模

Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling

原文发布日期：26 October 2023

DOI: 10.3390/cancers15215148

类型: Article

开放获取: 是

英文摘要：

Bone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated in drug resistance. Through a sophisticated analysis of public expression data from unexpanded BM MSCs, we uncovered a positive association between iMSC signature expression and minimal residual disease. While in vitro expansion generally results in the loss of the iMSC signature, our meta-analysis of additional public expression data demonstrated that cytokine stimulation, including IL1-β and TNF-α, as well as immune cells such as neutrophils, macrophages, and MM cells, can reactivate the signature expression of iMSCs to varying extents. These findings underscore the importance and potential utility of cytokine stimulation in mimicking the gene expression signature of early passage of iMSCs for functional characterizations of their tumor-supportive roles in MM.

摘要翻译： 

骨髓间充质干细胞（BM MSCs）在多发性骨髓瘤（MM）中通过促进耐药性和疾病复发发挥肿瘤支持作用。近期研究发现，在MM骨髓微环境中存在一种独特的MSCs亚群，称为炎症性MSCs（iMSCs），该亚群与耐药性密切相关。通过对未扩增骨髓MSCs的公共表达数据进行深入分析，我们发现iMSCs特征表达与微小残留病呈正相关。虽然体外扩增通常会导致iMSCs特征丢失，但我们对其他公共表达数据的荟萃分析表明，细胞因子刺激（包括IL1-β和TNF-α）以及中性粒细胞、巨噬细胞和MM细胞等免疫细胞，均能在不同程度上重新激活iMSCs的特征表达。这些发现强调了细胞因子刺激在模拟早期传代iMSCs基因表达特征方面的重要性及潜在应用价值，有助于进一步揭示其在MM中肿瘤支持功能的作用机制。

原文链接：

Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling