Bioprinted Glioblastoma Organoids

Remarkable advancements have been made in the ability to print complex tissue, including 3D model of Glioblastomas and other cancers. In 2019 Yi et al. published a new approach for creating a 3D bio-printed glioblastoma-on-a-chip model from patient derived cells that contain multiple cell types, different tumor components and hypoxic gradients (1).

Bio printing glioblastomas

To accomplish this, Yi and team combined dissociated GBM cells from resected tumors with a decellularized porcine `bio ink´ brain composed of Extra cellular matrix proteins. After bioprinting GBM cells, they printed a layer of human umbilical vein endothelial cells with the same porcine bio ink. Imaging of GBM cells labelled with a fluorescent dye showed evidence of invasion into surrounding endothelial cells. Immunostaining of pimonidazole (PM) a marker of hypoxia reveled a hypoxic gradient throughout the bio printed organoid. These features suggest that bio printed GBM organoid recapitulate important tumor features (1).

Strengths and weaknesses of a bio printed model

The bio printed model balances the benefits of other organoid models by providing a defined brain extracellular matrix to mimic the brain micro-environment, multiple cell types and defined tumor regions. The most important strength of this model is the short timeframe and scalability, making it particularly amenable to drug screening. Future advancements in biomedical engineering are sure to improve on this model, as it lacks normal brain tissue, imprecision of printing, homogeneity of printing substrates and the need for specialized equipment. (2,3).

References

1. Yi, H.-G., Jeong, Y. H., Kim, Y., Choi, Y.-J., Moon, H. E., Park, S. H., et al. (2019). A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat. Biomed. Eng. 3, 509–519. doi: 10.1038/s41551-019-0363-x

2. Maloney, E., Clark, C., Sivakumar, H., Yoo, K., Aleman, J., Rajan, S. A. P., et al. (2020). Immersion bioprinting of tumor organoids in multi-well plates for increasing chemotherapy screening throughput. Micromachines 11:208. doi: 10.3390/mi11020208

3. Tang, M., Xie, Q., Gimple, R. C., Zhong, Z., Tam, T., Tian, J., et al. (2020). Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions. Cell Res. 30, 833–853. doi: 10.1038/s41422-020-0338-1