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A tumorigenicity evaluation platform for cell therapies based on brain organoids
Jun Xue1,2, Youjun Chu3, Yanwang Huang1,2
1Department of Neurosurgery, Huashan Hospital, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200040, China.
Translational Neurodegeneration
|October 30, 2024
Summary
Brain organoids, particularly glioblastoma-like organoids, show promise for evaluating stem cell therapy risks. These models enhance detection of tumorigenic cells, potentially replacing animal testing for safety assessments.
Area of Science:
- Stem cell biology
- Neuroscience
- Biotechnology
Background:
- Tumorigenicity is a major hurdle in stem cell therapies, necessitating reliable evaluation methods.
- Current animal models for tumorigenicity assessment have significant limitations.
- Brain organoids offer a complex human-like model for neuroscience research, but their utility for tumorigenicity testing requires further investigation.
Purpose of the Study:
- To evaluate the capacity of brain organoids for assessing the tumorigenic potential of stem cells.
- To compare the sensitivity of cerebral organoids and glioblastoma-like (GBM) organoids for detecting tumorigenic cells.
- To explore the potential of brain organoids as an alternative to animal models for stem cell safety evaluations.
Main Methods:
- Human pluripotent stem cells (hPSCs) were used to generate cerebral organoids and GBM organoids (from TP53-/-/PTEN-/- hPSCs).
- Midbrain dopamine (mDA) cells, hPSCs, and immature mDA cells were injected into cerebral organoids, GBM organoids, and NOD SCID mice.
- Injected cells were characterized, and single-cell RNA sequencing was performed to compare organoid models.
Main Results:
- Both cerebral and GBM organoids supported mDA cell maturation.
- GBM organoids significantly enhanced the proliferation of hPSCs and immature mDA cells compared to cerebral organoids and mice.
- GBM organoids demonstrated superior sensitivity in detecting and evaluating the tumorigenic potential of spiked hPSCs, with upregulated tumor-related pathways.
Conclusions:
- Brain organoids serve as a viable platform for evaluating tumorigenic risk in stem cell therapies.
- GBM organoids provide a highly sensitive model that could complement or replace traditional animal-based tumorigenicity evaluations.
