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骨髓增生异常综合征中骨髓间充质干细胞的生物学特性。

Biologic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes.

机构信息

Department of Hematology, University of Crete School of Medicine, Heraklion, Crete, Greece.

出版信息

Curr Stem Cell Res Ther. 2011 Jun;6(2):122-30. doi: 10.2174/157488811795495422.

Abstract

Myelodysplastic syndromes comprise a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by ineffective bone marrow (BM) hematopoiesis, peripheral blood cytopenias and substantial risk for progression to acute myeloid leukemia. It is generally accepted that myelodysplastic syndromes originate as a result of multistep leukemogenesis, implicating genetic, epigenetic and immune-mediated alterations of an early hematopoietic stem cell. However, alterations in the BM microenvironment in terms of abnormal hematopoietic-to-stromal cell interactions, relative deficiency of hematopoietic growth factors and aberrant release of inhibitors may also have a role in myelodysplastic syndrome (MDS) pathogenesis. The possible involvement of the BM mesenchymal stem cells (MSC) in the pathogenetic/pathophysiologic process of MDS has been recently studied but existing data on MSCs' cytogenetic and functional integrity are controversial. Notably, in our study we did not find any significant quantitative or qualitative deficits in MDS-derived MSCs. As no conclusive data on the characteristics of BM MSCs have been reported so far, future studies should aim at elucidating whether BM MSCs belong primarily to the abnormal clone or whether they are indirectly damaged and whether they might be safely used for therapeutic purposes in MDS patients. This article aims to give an overview of the current state of the art on the quantitative, functional, immunoregulatory and cytogenetic properties of BM MSCs in MDS.

摘要

骨髓增生异常综合征是一组异质性克隆性造血干细胞恶性肿瘤,其特征为无效的骨髓(BM)造血、外周血细胞减少以及向急性髓系白血病进展的高风险。通常认为,骨髓增生异常综合征是由于多步骤白血病发生引起的,涉及早期造血干细胞的遗传、表观遗传和免疫介导改变。然而,BM 微环境中的改变,如异常造血细胞与基质细胞的相互作用、造血生长因子相对缺乏以及抑制剂的异常释放,也可能在骨髓增生异常综合征(MDS)发病机制中起作用。骨髓间充质干细胞(MSC)在 MDS 发病机制中的可能作用最近已经得到研究,但关于 MSC 细胞遗传学和功能完整性的现有数据存在争议。值得注意的是,在我们的研究中,我们没有发现 MDS 来源的 MSC 存在任何明显的数量或质量缺陷。由于迄今为止尚未报告关于 BM MSC 特征的明确数据,因此未来的研究应旨在阐明 BM MSC 主要属于异常克隆,还是它们受到间接损伤,以及它们是否可以安全地用于 MDS 患者的治疗目的。本文旨在概述 MDS 中 BM MSC 的定量、功能、免疫调节和细胞遗传学特性的最新研究进展。

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