文章：

人骨髓基质细胞系静脉共给药对免疫缺陷小鼠长期再生骨髓增生异常综合征细胞移植的影响

Effect of intravenous coadministration of human stroma cell lines on engraftment of long-term repopulating clonal myelodysplastic syndrome cells in immunodeficient mice

原文发布日期：2013-04-26

DOI: 10.1038/bcj.2013.11

类型: Original Article

开放获取: 是

英文摘要：

Engraftment of clonal hematopoietic precursor cells from patients with myelodysplastic syndrome (MDS) in immunodeficient mice has been difficult to achieve by intravenous (i.v.) injection. We used i.v. coadministration of the human marrow stroma cell line HS27a with CD34+ MDS cells in Nod.cg-Prkdcscid Il2rgtm1wjll (NSG) mice to provide signals that would facilitate engraftment. Hematopoietic cells from 24 MDS patients were transplanted. Cells from all patients were engrafted, and engraftment was documented in 44 of 46 evaluable mice (95%). Immunohistochemistry revealed human HS27a stroma colocalizing with human hematopoietic cells in mouse spleens. Human CD34+ precursors harvested from marrow and spleen of primary murine recipients, when combined with HS27a cells, were also engrafted successfully in secondary NSG recipients, showing persistence of the original clonal characteristics. This observation supports the concept that clonal markers were present in long-term repopulating cells. We suggest that HS27a stroma cells ‘traveled’ in direct contact with hematopoietic precursors and enabled their propagation. An essential signal for engraftment appears to be CD146, which is prominently expressed on HS27a cells. This xenotransplantation model will allow to further dissect signals that control engraftment of MDS cells and should be amenable to in vivo treatment studies.

摘要翻译： 

骨髓增生异常综合征（MDS）患者来源的克隆性造血前体细胞通过静脉注射途径在免疫缺陷小鼠体内实现植入一直难以成功。本研究采用将人骨髓基质细胞系HS27a与CD34+ MDS细胞通过静脉共移植至Nod.cg-Prkdcscid Il2rgtm1wjll（NSG）小鼠体内，以提供促进植入所需的信号。共移植了24例MDS患者的造血细胞，所有患者来源的细胞均成功植入，46只可评估小鼠中有44只（95%）观察到植入证据。免疫组化分析显示人HS27a基质细胞与人造血细胞共同定位于小鼠脾脏。从初代移植小鼠骨髓和脾脏中获取的人CD34+前体细胞，在与HS27a细胞联合移植后，也能在次级NSG受体中成功植入，并保持原始克隆特征。该发现证实克隆标志物存在于长期重建造血细胞中。我们认为HS27a基质细胞通过与造血前体细胞直接接触"伴随迁移"，促进其增殖。CD146分子似乎是实现植入的关键信号，该分子在HS27a细胞中高表达。这种异种移植模型将有助于进一步解析调控MDS细胞植入的关键信号，并为开展体内治疗研究提供平台。

原文链接：

Effect of intravenous coadministration of human stroma cell lines on engraftment of long-term repopulating clonal myelodysplastic syndrome cells in immunodeficient mice