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Through our support of the International Foundation for Ethical Research (IFER), NAVS is funding the development of human-relevant, cell-based models as powerful alternatives to animal experiments. We see great promise in models, such as organoids, that mimic the structure and function of real tissues and organs in reducing and replacing the use of animals in science.

In this week’s Science First, we’d like to share with you a new study that has been published regarding the utility of organoids for purposes ranging from organ development to research regarding diseased states.

Organoids are multicellular stem-cell derived models that form when stem cells self-assemble and organize into complex 3D structures. Organoids of several organs and tissues—including the human brain—have been developed.

While researchers use organoids for studying brain development and disease, there were concerns about whether organoids would be able to mature past mid-to late-fetal stages, which could limit their use. But a new study has demonstrated that, given time, the cells within organoids can display genetic signatures of cells after birth, broadening the developmental stages and brain disorders that organoids can model.

Researchers at Stanford University and the University of California, Los Angeles, teamed up to examine how organoids changed over time, given that some organoids can live for years. Beginning with human stem cells, the researchers created organoids to model the human brain. They periodically removed some cells to determine which genes were active, and they compared organoid gene activity to the gene activity of cells from human brains at different ages.

Interestingly, when the brain organoids reached a significant milestone, approximately nine months old, their gene expression changed and more closely matched the cells of human brains shortly after birth. Other changes associated with mature human brain cells were observed as the organoids aged as well. This is an exciting discovery, given that this timeframe parallels development in vivo.

The researchers also looked at the expression of genes linked to different brain disorders, including Alzheimer’s disease, schizophrenia and epilepsy to identify when they may affect brain development. This knowledge may help identify a particular time frame in which an organoid might best model these disorders.

The study is changing the mindset of some researchers about what kind of research organoids can be used for. According to developmental geneticist Madeline Lancaster, “Things that, before I saw this paper, I would have said you can’t do with organoids…actually, maybe you can.”

While some technical challenges remain with organoids, we are optimistic that these in vitro tools will have a significant effect on reducing and replacing animal use in science.

Sources:

Gordon, A., et al. “Long-term maturation of human cortical organoids matches key early postnatal transitions.” Nature Neuroscience, Feb. 22, 2021.

Servick, K. “Brain cell clusters, grown in lab for more than a year, mirror changes in a newborn’s brain.” Science, Feb. 22, 2021.