衰老的间充质干细胞促进骨髓增生异常综合征的进展

Senescent Mesenchymal Stem Cells Contributeto Progression of Myelodysplastic Syndromes——Review

骨髓增生异常综合征(MDS)是一组恶性造血干细胞疾病,以无效造血并向急性髓系白血病(AML)转化为主要特点。MDS克隆细胞获得增殖优势和促使疾病进展的因素尚不清楚。大量实验表明,骨髓微环境中的间充质干细胞(MSC)的异常导致MDS的发生并促进疾病向AML转化。MDS来源的MSC存在衰老现象,其遗传学、表观遗传学及基因的表达异常,导致其形态、增殖、分化、分泌功能改变,致使其支持正常造血功能下降,促进疾病向AML转化。对MDS中克隆细胞和MSC均有作用的药物临床实验结果令人满意,这说明干预MDS造血细胞和间质细胞相互作用可能成为治疗MDS的一种新的治疗途径。本文就MDS治疗现状、MDS-MSC衰老及表型特点、衰老MDS-MSC支持造血功能的变化。MDS-MSC在MDS预后中的意义及MDS-MSC作为MDS治疗的潜在靶点作一综述。

Myelodysplastic syndromes（ MDS） comprise a group of malignant hematopoietic stem cell（ HSC） disorders characterized by ineffective hematopoiesis.The risk of transformation to acute myeloid leukemia（ AML） is increasing.The initiating event in HSC of MDS leads to a growth advantage and subsequent clonal expansion, that is still poorly understood.Accumulating data indicate that the mesenchymal stem cells（ MSCs） in MDS model display aberrant characteristics contributing to disease initiation and transformation into AML.MSC derived from MDS displayed the alteration in genetics,epigenetics and gene expression,which contribute to altered morphology,impaired proliferative and differentiation capacity and perturbed cytokine secretions,thus destroy in their ability to support normal hematopoiesis and contribute to malignant progression.A number of promising agents that target the interactions of the MDS clone with MSC are currently investigated in various phases of clinical trial,that might ultimately result in novel therapeutic strategies,targeting niche cells to attenuate leukemic progression.In this article, the current status of MDS treatment, the characteristics of MDS-MSC senescence and phenotypes,the changes of hematopoietic function sapported by senescent MDS-MSC,the significane of MDS-MSC in MDS prognosis and the MDS-MSC as potential target for treatment of MDS are summarized.