Eroz Ilayda, Kakkar Prabneet Kaur, Lazar Renal Antoinette, El-Jawhari Jehan
Biosciences Department, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK.
Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Biomedicines. 2024 Jul 26;12(8):1677. doi: 10.3390/biomedicines12081677.
Mesenchymal stem cells (MSCs) are one of the main residents in the bone marrow (BM) and have an essential role in the regulation of haematopoietic stem cell (HSC) differentiation and proliferation. Myelodysplastic syndromes (MDSs) are a group of myeloid disorders impacting haematopoietic stem and progenitor cells (HSCPs) that are characterised by BM failure, ineffective haematopoiesis, cytopenia, and a high risk of transformation through the expansion of MDS clones together with additional genetic defects. It has been indicated that MSCs play anti-tumorigenic roles such as in cell cycle arrest and pro-tumorigenic roles including the induction of metastasis in MDS and leukaemia. Growing evidence has shown that MSCs have impaired functions in MDS, such as decreased proliferation capacity, differentiation ability, haematopoiesis support, and immunomodulation function and increased inflammatory alterations within the BM through some intracellular pathways such as Notch and Wnt and extracellular modulators abnormally secreted by MSCs, including increased expression of inflammatory factors and decreased expression of haematopoietic factors, contributing to the development and progression of MDSs. Therefore, MSCs can be targeted for the treatment of MDSs and leukaemia. However, it remains unclear what drives MSCs to behave abnormally. In this review, dysregulations in MSCs and their contributions to myeloid haematological malignancies will be discussed.
间充质干细胞(MSCs)是骨髓(BM)中的主要驻留细胞之一,在造血干细胞(HSC)的分化和增殖调节中起着至关重要的作用。骨髓增生异常综合征(MDSs)是一组影响造血干细胞和祖细胞(HSCPs)的髓系疾病,其特征为骨髓衰竭、无效造血、血细胞减少,以及通过MDS克隆的扩增和其他遗传缺陷而具有高转化风险。已有研究表明,MSCs在MDS和白血病中发挥着抗肿瘤作用,如细胞周期阻滞,也发挥着促肿瘤作用,包括诱导转移。越来越多的证据表明,MSCs在MDS中功能受损,如增殖能力、分化能力、造血支持能力和免疫调节功能下降,以及通过Notch和Wnt等一些细胞内途径和MSCs异常分泌的细胞外调节因子导致骨髓内炎症改变增加,包括炎症因子表达增加和造血因子表达减少,这有助于MDS的发生和发展。因此,MSCs可作为治疗MDS和白血病的靶点。然而,尚不清楚是什么导致MSCs行为异常。在这篇综述中,将讨论MSCs的失调及其对髓系血液系统恶性肿瘤的影响。