1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] School of Medicine, Jiangnan University, Wuxi, China.
Blood Cancer J. 2013 Apr 26;3(4):e113. doi: 10.1038/bcj.2013.11.
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-Prkdc(scid) Il2rg(tm1wjll) (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.
在免疫缺陷小鼠中，通过静脉（i.v.）注射难以实现骨髓增生异常综合征（MDS）患者的克隆造血前体细胞的植入。我们使用人骨髓基质细胞系 HS27a 与 CD34+ MDS 细胞的 i.v. 共给药，为植入提供促进信号。移植了 24 位 MDS 患者的造血细胞。所有患者的细胞均被植入，46 只可评估小鼠中有 44 只（95%）记录到植入。免疫组织化学显示人 HS27a 基质与小鼠脾脏中的人造血细胞共定位。从原发性小鼠受者的骨髓和脾脏中收获的人 CD34+前体与 HS27a 细胞结合后，也成功地植入了二次 NSG 受者，显示出原始克隆特征的持续存在。这一观察结果支持了克隆标记存在于长期重建造血细胞中的概念。我们建议 HS27a 基质细胞“直接接触”造血前体并促进其增殖。植入的一个重要信号似乎是 CD146，它在 HS27a 细胞上高度表达。这种异种移植模型将允许进一步剖析控制 MDS 细胞植入的信号，并且应该适合体内治疗研究。
