Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: the importance of reproducing blood-brain barrier heterogeneity

高级别胶质瘤临床前小鼠模型在纳米医学研究中的比较研究:重现血脑屏障异质性的重要性

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作者:Caterina Brighi, Lee Reid, Laura A Genovesi, Marija Kojic, Amanda Millar, Zara Bruce, Alison L White, Bryan W Day, Stephen Rose, Andrew K Whittaker, Simon Puttick

Conclusion

The WK1 mouse model more accurately reproduces the extent of BBB disruption, the level of BBB permeability and the histopathological characteristics found in rHGG patients than the U87 mouse model, and is therefore a more clinically relevant model for preclinical evaluations of emerging nanoparticle-based therapies for HGG.

Results

The extent of BBB disruption and permeability in the contrast enhancing tumor was significantly higher in the U87 model than in rHGG. These values in the WK1 model are similar to those of rHGG. The U87 model is not infiltrative, has an entirely abnormal and leaky vasculature and it is not of glial origin. The WK1 model infiltrates into the non-neoplastic brain parenchyma, it has both regions with intact BBB and regions with leaky BBB and remains of glial origin.

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