Preferential inactivation of paediatric solid tumour cells by sequential exposure to Merocyanine 540-mediated photodynamic therapy and Edelfosine: implications for the ex vivo purging of autologous haematopoietic stem cell grafts
Preferential inactivation of paediatric solid tumour cells by sequential exposure to Merocyanine 540-mediated photodynamic therapy and Edelfosine: implications for the ex vivo purging of autologous haematopoietic stem cell grafts
复制标题
DOI：
10.1016/s1011-1344(02)00411-6
复制
发表时间：
2003-02-01
影响因子：
5.4
通讯作者：
Sieber, F
中科院分区：
文献类型：
--
作者：
Anderson, GS;Tsujino, I;Sieber, F
儿童实体瘤对烷基化剂表现出陡峭的剂量反应曲线，因此被认为是高剂量化疗和自体干细胞支持的候选者。越来越多的证据表明，来自实体瘤患者的自体干细胞移植物经常被活的肿瘤细胞污染。本研究的目的是在临床前净化模型中，对Merocyanine 540介导的光动力疗法（MC540-PDT）与短暂暴露于烷酰溶血磷脂Edelfosine的两步净化程序的安全性和有效性进行初步评估。将人类和小鼠骨髓细胞、神经-2a小鼠神经母细胞瘤、SK-N-SH人类神经母细胞瘤、SK-ES-1和U-2 OS人类骨肉瘤、G-401和SK-NEP-1人类威尔姆斯瘤和a -204人类横纹肌肉瘤细胞暴露于固定剂量的MC540-PDT中，然后用浓度分级的雪绒花进行短暂孵育。随后通过体外克隆测定或在cd34阳性造血干细胞的情况下，通过免疫组织化学方法评估存活。MC540-PDT和Edelfosine联合清除使所有肿瘤细胞减少bbbb4 log，同时保留至少15%的小鼠粒细胞/巨噬细胞祖细胞（CFU-GM）， 34%的人CFU-GM和31%的人cd34阳性细胞。数据表明，MC540-PDT和Edelfosine联合清除可能对儿童实体瘤患者的自体干细胞移植物的体外清除有用。(C) 2002 Elsevier Science B.V.版权所有
Paediatric solid tumours exhibit steep dose-response curves to alkylating agents and are therefore considered candidates for high-dose chemotherapy and autologous stem cell support. There is growing evidence that autologous stem cell grafts from patients with solid tumours are frequently contaminated with live tumour cells. The objective of this study was to perform, in a preclinical purging model, an initial assessment of the safety and efficacy of a two-step purging procedure that combined Merocyanine 540-mediated photodynamic therapy (MC540-PDT) with a brief exposure to the alkyl-lysophospholipid, Edelfosine. Human and murine bone marrow cells and Neuro-2a murine neuroblastoma, SK-N-SH human neuroblastoma, SK-ES-1 and U-2 OS human osteosarcoma, G-401 and SK-NEP-1 human Wilms' tumour, and A-204 human rhabdomyosarcoma cells were exposed to a fixed dose of MC540-PDT followed by a brief incubation with graded concentrations of Edelfosine. Survival was subsequently assessed by in vitro clonal assay or, in the case of CD34-positive haematopoietic stem cells, by an immunohistochemical method. Combination purging with MC540-PDT and Edelfosine depleted all tumour cells by >4 log while preserving at least 15% of murine granulocyte/macrophage progenitors (CFU-GM), 34% of human CFU-GM, and 31% of human CD34-positive cells. The data suggest that combination purging with MC540-PDT and Edelfosine may be useful for the ex vivo purging of autologous stem cell grafts from patients with paediatric solid tumours. (C) 2002 Elsevier Science B.V. All rights reserved.