Abstract
Glioblastoma (GBM) tumor cells are found in the perivascular niche microenvironment and are believed to associate closely with the brain microvasculature. However, it is largely unknown how the resident cells of the perivascular niche, such as endothelial cells, pericytes, and astrocytes, influence GBM tumor cell behavior and disease progression. A 3D in vitro model of the brain perivascular niche developed by encapsulating brain-derived endothelial cells, pericytes, and astrocytes in a gelatin hydrogel is described. It is shown that brain perivascular stromal cells, namely pericytes and astrocytes, contribute to vascular architecture and maturation. Cocultures of patient-derived GBM tumor cells with brain microvascular cells are used to identify a role for pericytes and astrocytes in establishing a perivascular niche environment that modulates GBM cell invasion, proliferation, and therapeutic response. Engineered models provide unique insight regarding the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche. Critically, it is shown that engineered perivascular models provide an important resource to evaluate mechanisms by which intercellular interactions modulate GBM tumor cell behavior, drug response, and provide a framework to consider patient-specific disease phenotypes.
Overview
- The study aims to investigate the role of brain perivascular stromal cells in modulating GBM tumor cell behavior and disease progression. The study uses a 3D in vitro model of the brain perivascular niche to evaluate the influence of pericytes and astrocytes on GBM cell invasion, proliferation, and therapeutic response. The study also aims to identify the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche. The hypothesis being tested is that brain perivascular stromal cells contribute to the perivascular niche environment that modulates GBM cell behavior and disease progression. The methodology used for the experiment includes the development of a 3D in vitro model of the brain perivascular niche using brain-derived endothelial cells, pericytes, and astrocytes encapsulated in a gelatin hydrogel. The study also includes cocultures of patient-derived GBM tumor cells with brain microvascular cells to identify the role of pericytes and astrocytes in establishing a perivascular niche environment that modulates GBM cell behavior and disease progression. The primary objective of the study is to provide insight into the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche and to identify the role of brain perivascular stromal cells in modulating GBM cell behavior and disease progression.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies that brain pericytes and astrocytes contribute to vascular architecture and maturation in the brain perivascular niche. Cocultures of patient-derived GBM tumor cells with brain microvascular cells show that pericytes and astrocytes establish a perivascular niche environment that modulates GBM cell invasion, proliferation, and therapeutic response. The study also identifies the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche. The key findings of the study are that brain pericytes and astrocytes contribute to vascular architecture and maturation in the brain perivascular niche and that they establish a perivascular niche environment that modulates GBM cell behavior and disease progression. The study also identifies the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study provides insight into the role of brain perivascular stromal cells in modulating GBM tumor cell behavior and disease progression. The study also identifies the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche. The study's findings suggest that intercellular interactions between brain perivascular stromal cells and GBM tumor cells play a critical role in modulating GBM cell behavior and disease progression. The study's findings also suggest that the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche is critical for understanding the disease's progression and developing effective therapies. The study's limitations include the use of patient-derived GBM tumor cells, which may not fully represent the heterogeneity of GBM tumors. Future research directions include the use of genetically engineered models to study the role of specific genes in modulating GBM cell behavior and disease progression. The study also suggests the need for further research to identify the specific mechanisms by which intercellular interactions modulate GBM cell behavior and disease progression.