文章：

来自Shwachman-Diamond综合征患者的间充质干细胞显示正常功能，不会导致血液系统缺陷

Mesenchymal stem cells from Shwachman–Diamond syndrome patients display normal functions and do not contribute to hematological defects

原文发布日期：2012-10-12

DOI: 10.1038/bcj.2012.40

类型: Original Article

开放获取: 是

英文摘要：

Shwachman–Diamond syndrome (SDS) is a rare inherited disorder characterized by bone marrow (BM) dysfunction and exocrine pancreatic insufficiency. SDS patients have an increased risk for myelodisplastic syndrome and acute myeloid leukemia. Mesenchymal stem cells (MSCs) are the key component of the hematopoietic microenvironment and are relevant in inducing genetic mutations leading to leukemia. However, their role in SDS is still unexplored. We demonstrated that morphology, growth kinetics and expression of surface markers of MSCs from SDS patients (SDS-MSCs) were similar to normal MSCs. Moreover, SDS-MSCs were able to differentiate into mesengenic lineages and to inhibit the proliferation of mitogen-activated lymphocytes. We demonstrated in an in vitro coculture system that SDS-MSCs, significantly inhibited neutrophil apoptosis probably through interleukin-6 production. In a long-term coculture with CD34+-sorted cells, SDS-MSCs were able to sustain CD34+ cells survival and to preserve their stemness. Finally, SDS-MSCs had normal karyotype and did not show any chromosomal abnormality observed in the hematological components of the BM of SDS patients. Despite their pivotal role in the hematopoietic stem cell niche, our data suggest that MSC themselves do not seem to be responsible for the hematological defects typical of SDS patients.

摘要翻译： 

Shwachman-Diamond综合征（SDS）是一种罕见的遗传性疾病，以骨髓功能障碍和外分泌胰腺功能不全为特征。SDS患者发生骨髓增生异常综合征和急性髓系白血病的风险增高。间充质干细胞（MSCs）是造血微环境的关键组分，与诱发白血病发生的基因突变相关。然而，其在SDS中的作用尚未明确。我们发现SDS患者来源的MSCs（SDS-MSCs）在形态、生长动力学及表面标志物表达方面与正常MSCs相似。此外，SDS-MSCs能够向中胚层谱系分化，并可抑制丝裂原活化淋巴细胞的增殖。在体外共培养体系中，我们证实SDS-MSCs可能通过白细胞介素-6的产生显著抑制中性粒细胞凋亡。在与CD34+分选细胞的长期共培养中，SDS-MSCs能够维持CD34+细胞存活并保留其干性。最后，SDS-MSCs具有正常核型，且未表现出在SDS患者骨髓造血组分中观察到的任何染色体异常。尽管MSCs在造血干细胞微环境中起核心作用，我们的数据表明MSCs本身似乎并非导致SDS患者典型血液学缺陷的原因。

原文链接：

Mesenchymal stem cells from Shwachman–Diamond syndrome patients display normal functions and do not contribute to hematological defects