Modeling Human Brain Tumors and the Microenvironment Using Induced Pluripotent Stem Cells

Abstract

Brain cancer is a group of diverse and rapidly growing malignancies that originate in the central nervous system (CNS) and have a poor prognosis. The complexity of brain structure and function makes brain cancer modeling extremely difficult, limiting pathological studies and therapeutic developments. Advancements in human pluripotent stem cell technology have opened a window of opportunity for brain cancer modeling, providing a wealth of customizable methods to simulate the disease in vitro. This is achieved with the advent of genome editing and genetic engineering technologies that can simulate germline and somatic mutations found in human brain tumors. This review investigates induced pluripotent stem cell (iPSC)-based approaches to model human brain cancer. The applications of iPSCs as renewable sources of individual brain cell types, brain organoids, blood–brain barrier (BBB), and brain tumor models are discussed. The brain tumor models reviewed are glioblastoma and medulloblastoma. The iPSC-derived isogenic cells and three-dimensional (3D) brain cancer organoids combined with patient-derived xenografts will enhance future compound screening and drug development for these deadly human brain cancers.

Modeling human brain rhabdoid tumor by inactivating tumor suppressor genes in induced pluripotent stem cells

“…Brain organoids resembling distinct brain regions have been successfully developed in vitro using chemical and physical inductions to form a 3D culture, which allows for cell-cell and cell-matrix interaction and physiological activities [ [23] , [24] , [25] ]. These organoids present an excellent platform for neurological disease modeling and drug screening [ 26 ]. Genetically engineered cerebral organoids derived from hiPSCs could recapitulate every glioblastoma subtype [ 27 ]; however, hiPSC-derived ATRT tumor models are yet elusive.…”

Preclinical Models of Neuroblastoma—Current Status and Perspectives

“…Importantly, none of these techniques fully recapitulate the process of carcinogenesis and cancer progression. Hence, they can be optimized and combined to complement each other, and thereby provide reliable tissue and organ models [ 30 , 31 , 32 , 33 , 34 ]. Currently, morphologically and genetically accurate complex in vitro models (CIVMs) are being developed to enable studies on particular cancer types [ 35 ].…”