Reserves, Functional, Immunoregulatory, and Cytogenetic Properties of Bone Marrow Mesenchymal Stem Cells in Patients with Myelodysplastic Syndromes
Reserves, Functional, Immunoregulatory, and Cytogenetic Properties of Bone Marrow Mesenchymal Stem Cells in Patients with Myelodysplastic Syndromes
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DOI：
10.1089/scd.2009.0286
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发表时间：
2010-07-01
影响因子：
4
通讯作者：
Papadaki, Helen A.
中科院分区：
文献类型：
--
作者：
Klaus, Mirjam;Stavroulaki, Emily;Papadaki, Helen A.
骨髓基质的造血支持能力缺陷与骨髓增生异常综合征（MDS）的病理生理学有关。本研究的目的是通过评估初发MDS患者（n = 13）的储备、功能特性以及细胞遗传学特征，并与骨髓造血细胞进行比较，探讨骨髓基质祖细胞，即间充质干细胞（MSCs）在MDS中是否受到主要影响。患者和正常人（n = 20）的间充质干细胞在数量、向脂肪细胞/软骨细胞/成骨细胞分化的潜能以及在抑制有丝分裂原诱导的T细胞增殖方面的免疫抑制功能上没有显著差异。患者的间充质干细胞在促炎或促生长细胞因子的产生方面没有显示出任何异常，也没有携带造血细胞中存在的细胞遗传学异常。然而，偶尔患者和正常人的间充质干细胞培养会出现不相关的染色体改变（5号和7号染色体三体），其病理生理意义不确定。与对照组相比，患者的间充质干细胞在传代过程中表现出增殖和克隆形成能力受损，这可能代表一种与患者骨髓中存在的慢性炎症过程相关的非特异性异常。这些数据表明，MDS患者的骨髓间充质干细胞不属于异常克隆，也不是导致炎症性骨髓微环境的主要细胞来源。
Defective hematopoiesis supporting capacity of bone marrow (BM) stroma has been implicated in the pathophysiology of myelodysplastic syndromes (MDS). The aim of this study is to explore whether the BM stroma progenitors, namely the mesenchymal stem cells (MSCs), are primarily affected in MDS by evaluating the reserves, the functional properties, as well as the cytogenetic characteristics, in comparison to BM hematopoietic cells, in patients with de novo MDS (n = 13). The number, differentiation potential toward adipocytes/chondrocytes/osteoblasts and immunosuppressive function in terms of inhibition of mitogen-induced T-cell proliferation did not differ significantly between patient and normal (n = 20) MSCs. Patient MSCs did not show any aberrations in the production of proinflammatory or growth-promoting cytokines and did not harbor the cytogenetic abnormalities present in hematopoietic cells. Occasional patient and normal MSC cultures, however, developed irrelevant chromosomal alterations (trisomies 5 and 7) with uncertain pathophysiologic significance. Compared to controls, patient MSCs displayed impaired proliferative and clonogenic potential through passages that might represent a nonspecific abnormality associated with the chronic inflammatory process present in patients' BM. These data suggest that BM MSCs from MDS patients do not belong to the abnormal clone and do not represent the main cellular source contributing to the inflammatory marrow microenvironment.