Rapidly Developing Organoid Technology

Organoid technology is improving rapidly with effective incorporation of immune cells and vascularization, which often represents the major hurdles in this technology. Other advancements are to facilitate new discovery research and drug development efforts.

Glioblastoma is known to invade along the perivascular space. Glioblastoma (GBM) also referred to as grade 4 astrocytoma, it is a fast growing and aggressive tumor. It invades the nearby brain tissue but does not spread to distant organs. Therefore, vascularized organoid-GMB-co-cultures, would be an intriguing model to study invasive behaviors and potential therapies to prevent perivascular invasion (1,2).

Brain Organoids

Additionally, multiple brain region-specific organoid protocols have now been standardized and it would be interesting to determine how the behavior of GMB differs within different brain region-specific microenvironments. A limitation of brain organoid differential protocol is that they produce relatively immature neurons and glia and a high percentage of replicating progenitor cells, as compared to developed human brains. Even the most mature and long-cultured brain organoids resemble fetal brain tissue. This is not unique to brain organoids and efforts have been made to artificially age iPSC-based cultures genetically or pharmacologically. (3,4).

Compound screening with 3D models is an emerging field, but till date, tumor organoids are primarily used for compound screening. Although some of have used patient-derived GBM organoids to validate hits from higher-throughput in vitro compound screens (5).

参考文献

1. 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

2. Scherer, H. J. (1938). Structural development in gliomas. Am. J. Cancer 34, 333–351. doi: 10.1158/ajc.1938.333

3. Miller, J. D., Ganat, Y. M., Kishinevsky, S., Bowman, R. L., Liu, B., Tu, E. Y., et al. (2013). Human IPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13, 691–705. doi: 10.1016/j.stem.2013.11.006

4. Garcia, T. Y., Gutierrez, M., Reynolds, J., and Lamba, D. A. (2015). Modeling the dynamic AMD-associated chronic oxidative stress changes in human ESC and Ipsc-derived RPE cells. Invest. Ophthal. Vis. Sci. 56, 7480–7488. doi: 10.1167/iovs.15-17251

5. Weeber, F., Ooft, S. N., Dijkstra, K. K., and Voest, E. E. (2017). Tumor organoids as a pre-clinical cancer model for drug discovery. Cell Chem. Biol. 24, 1092–1100. doi: 10.1016/j.chembiol.2017.06.012