CEREBRAL ORGANOIDS AS A MODEL FOR GLIOBLASTOMA MULTIFORME

Overview

Journal Curr Opin Biomed Eng

Specialty Biomedical Engineering

Date 2020 May 2

PMID 32355905

Citations 8

Authors

Nathaniel Silvia

Guohao Dai

Affiliations

Soon will be listed here.

Abstract

Glioblastoma multiforme (GBM) is a highly lethal and elusive cancer. While many and models have been developed to recapitulate the factors that contribute to its invasive behavior, they suffer from drawbacks related to genetic variability, expense and scope. Technologies utilizing human pluripotent stem cells can now generate organoids which can recapitulate the relative complexity the cytoarchitecture and microenvironment of human brain tissue. In conjunction with protocols which effectively induce GBM tumors within these "cerebral organoids", such approaches represent an unprecedented model to investigate GBM invasion and its effect on the brain ECM. This review focuses on methods of brain organoid development, protocols for inducing GBM, the relevant findings on invasion and microenvironmental changes, and discusses their limitations and potential future direction.

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References

Pasca A, Sloan S, Clarke L, Tian Y, Makinson C, Huber N . Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015; 12(7):671-8. PMC: 4489980. DOI: 10.1038/nmeth.3415. View

Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin N . Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 2006; 9(5):391-403. DOI: 10.1016/j.ccr.2006.03.030. View

Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M . Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1):98-110. PMC: 2818769. DOI: 10.1016/j.ccr.2009.12.020. View

Singh S, Clarke I, Terasaki M, Bonn V, Hawkins C, Squire J . Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003; 63(18):5821-8. View

Kadoshima T, Sakaguchi H, Nakano T, Soen M, Ando S, Eiraku M . Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc Natl Acad Sci U S A. 2013; 110(50):20284-9. PMC: 3864329. DOI: 10.1073/pnas.1315710110. View

Schmid R, Vitucci M, Miller C . Genetically engineered mouse models of diffuse gliomas. Brain Res Bull. 2011; 88(1):72-9. DOI: 10.1016/j.brainresbull.2011.06.002. View

Qian X, Nguyen H, Jacob F, Song H, Ming G . Using brain organoids to understand Zika virus-induced microcephaly. Development. 2017; 144(6):952-957. PMC: 5358105. DOI: 10.1242/dev.140707. View

Lee C, Bendriem R, Wu W, Shen R . 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. J Biomed Sci. 2017; 24(1):59. PMC: 5563385. DOI: 10.1186/s12929-017-0362-8. View

Eiraku M, Watanabe K, Matsuo-Takasaki M, Kawada M, Yonemura S, Matsumura M . Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell. 2008; 3(5):519-32. DOI: 10.1016/j.stem.2008.09.002. View

10.

Lu P, Weaver V, Werb Z . The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol. 2012; 196(4):395-406. PMC: 3283993. DOI: 10.1083/jcb.201102147. View

11.

AlFatah Mansour A, Goncalves J, Bloyd C, Li H, Fernandes S, Quang D . An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol. 2018; 36(5):432-441. PMC: 6331203. DOI: 10.1038/nbt.4127. View

12.

Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-96. DOI: 10.1056/NEJMoa043330. View

13.

de Vries N, Beijnen J, van Tellingen O . High-grade glioma mouse models and their applicability for preclinical testing. Cancer Treat Rev. 2009; 35(8):714-23. DOI: 10.1016/j.ctrv.2009.08.011. View

14.

Camp J, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Brauninger M . Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A. 2015; 112(51):15672-7. PMC: 4697386. DOI: 10.1073/pnas.1520760112. View

15.

Kelava I, Lancaster M . Dishing out mini-brains: Current progress and future prospects in brain organoid research. Dev Biol. 2016; 420(2):199-209. PMC: 5161139. DOI: 10.1016/j.ydbio.2016.06.037. View

16.

Rubenstein B, Kaufman L . The role of extracellular matrix in glioma invasion: a cellular Potts model approach. Biophys J. 2008; 95(12):5661-80. PMC: 2599859. DOI: 10.1529/biophysj.108.140624. View

17.

Hubert C, Rivera M, Spangler L, Wu Q, Mack S, Prager B . A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo. Cancer Res. 2016; 76(8):2465-77. PMC: 4873351. DOI: 10.1158/0008-5472.CAN-15-2402. View

18.

Nasu M, Takata N, Danjo T, Sakaguchi H, Kadoshima T, Futaki S . Robust formation and maintenance of continuous stratified cortical neuroepithelium by laminin-containing matrix in mouse ES cell culture. PLoS One. 2013; 7(12):e53024. PMC: 3534089. DOI: 10.1371/journal.pone.0053024. View

19.

Wurdak H . Exploring the cancer stem cell phenotype with high-throughput screening applications. Future Med Chem. 2012; 4(10):1229-41. DOI: 10.4155/fmc.12.73. View

20.

Pham M, Pollock K, Rose M, Cary W, Stewart H, Zhou P . Generation of human vascularized brain organoids. Neuroreport. 2018; 29(7):588-593. PMC: 6476536. DOI: 10.1097/WNR.0000000000001014. View