Fellenberg Joerg, Losch Sarina, Marinescu Max R, Frey Birgit, Lehner Burkhard, Arango-Ospina Marcela, Hadzhieva Zoya, Boccaccini Aldo R, Westhauser Fabian
Experimental Orthopaedics, Department of Orthopaedics, Heidelberg University Hospital, 69118 Heidelberg, Germany.
Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Cancers (Basel). 2023 Mar 20;15(6):1868. doi: 10.3390/cancers15061868.
Tumor recurrence is a major problem during the treatment of giant cell tumors of bone (GCTB). We recently identified tumor cell-specific cytotoxic effects of bioactive glasses (BGs) toward neoplastic stromal cells derived from GCTB tissue (GCTSCs) in vitro. Since these data indicated a promising role of BGs in the adjuvant treatment of GCTBs, we aimed to investigate the transferability of the in vitro data into the more complex in vivo situation in the current study. We first analyzed the cytotoxicity of three different BGs in vitro by WST-1 assay after co-cultivation with primary GCTSC cell lines. The effects of BGs on tumor engraftment and growth were analyzed by chicken chorioallantoic membrane (CAM) assays and subsequent quantification of tumor take rates and tumor volumes. In vitro, all tested BGs displayed a cytotoxic effect on GCTSCs that was dependent on BG composition, concentration, and particle size. Comparable effects could be observed within the in vivo environment resulting in reduced tumor take rates and tumor volumes in BG-treated samples. These data indicate a possible clinical application of BGs in the context of GCTB therapy, mediating a reduction of recurrence rates with the simultaneous promotion of bone regeneration.
肿瘤复发是骨巨细胞瘤(GCTB)治疗过程中的一个主要问题。我们最近在体外鉴定了生物活性玻璃(BGs)对源自GCTB组织的肿瘤基质细胞(GCTSCs)的肿瘤细胞特异性细胞毒性作用。由于这些数据表明BGs在GCTBs的辅助治疗中具有潜在作用,我们旨在研究在当前研究中如何将体外数据转化为更复杂的体内情况。我们首先通过与原代GCTSC细胞系共培养后用WST-1法分析了三种不同BGs的体外细胞毒性。通过鸡胚绒毛尿囊膜(CAM)试验以及随后对肿瘤接种率和肿瘤体积的定量分析,研究了BGs对肿瘤植入和生长的影响。在体外,所有测试的BGs对GCTSCs均表现出细胞毒性作用,且该作用取决于BG的组成、浓度和粒径。在体内环境中也观察到了类似的效果,导致BG处理样本的肿瘤接种率和肿瘤体积降低。这些数据表明BGs在GCTB治疗中可能具有临床应用价值,可在促进骨再生的同时降低复发率。