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Published on: August 23, 2016
Stem cell modeling of nervous system tumors
Frank B Furnari1, Corina Anastasaki2, Shan Bian3
1Department of Medicine, University of California, San Diego, San Diego, CA 92037, USA.
Abstract:
Nervous system tumors, particularly brain tumors, represent the most common tumors in children and one of the most lethal tumors in adults. Despite decades of research, there are few effective therapies for these cancers. Although human nervous system tumor cells and genetically engineered mouse models have served as excellent platforms for drug discovery and preclinical testing, they have limitations with respect to accurately recapitulating important aspects of the pathobiology of spontaneously arising human tumors. For this reason, attention has turned to the deployment of human stem cell engineering involving human embryonic or induced pluripotent stem cells, in which genetic alterations associated with nervous system cancers can be introduced. These stem cells can be used to create self-assembling three-dimensional cerebral organoids that preserve key features of the developing human brain. Moreover, stem cell-engineered lines are amenable to xenotransplantation into mice as a platform to investigate the tumor cell of origin, discover cancer evolutionary trajectories and identify therapeutic vulnerabilities. In this article, we review the current state of human stem cell models of nervous system tumors, discuss their advantages and disadvantages, and provide consensus recommendations for future research.
Insights
Human stem cell models, including cerebral organoids, offer a more accurate platform for studying nervous system tumors. These models aid in understanding cancer origins and identifying new therapeutic targets.
Area of Science:
- Neuro-oncology
- Stem cell biology
- Cancer research
Background:
- Nervous system tumors, including brain tumors, are a significant cause of mortality in both children and adults.
- Current therapeutic options for these cancers are limited, despite extensive research.
- Existing preclinical models, such as cell lines and mouse models, have limitations in fully replicating human nervous system tumor pathobiology.
Approach:
- Human stem cell engineering, utilizing embryonic or induced pluripotent stem cells, allows for the introduction of cancer-associated genetic alterations.
- These engineered stem cells can self-assemble into three-dimensional cerebral organoids, mimicking key aspects of human brain development.
- Stem cell-derived models facilitate xenotransplantation into mice for studying tumor origins, evolutionary paths, and therapeutic vulnerabilities.
Key Points:
- Human stem cell-based models, particularly cerebral organoids, provide a more faithful recapitulation of human nervous system tumor development.
- These models enable investigation into the cellular origins of nervous system cancers.
- They are instrumental in uncovering cancer evolutionary trajectories and identifying novel therapeutic targets.
Conclusions:
- Human stem cell models represent a significant advancement in nervous system tumor research, overcoming limitations of traditional models.
- Cerebral organoids and xenotransplantation platforms offer powerful tools for dissecting tumor pathobiology and discovering new treatments.
- Further research and consensus-driven recommendations are crucial for optimizing the use of these innovative models.
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