A National Institutes of Health-funded research team demonstrated that three-dimensional cell culture models of human brain tissue, called organoids, can continue developing and mature over an extended period, potentially enabling long-term laboratory studies of neurodevelopmental disorders.
Researchers at Harvard University led by Paola Arlotta sustained organoids for nearly six years and tracked their development using gene expression analysis and biological age assessment. The organoids exhibited the emergence and maturation of neurons and supporting glial cells, with developmental milestones occurring at the same pace as in the human brain, according to the study published August 19 in Nature.
Neurons established connections with each other and fired electrical signals that the organoids sustained for at least two years. The authors grew the tissue in a specialized fluid that supported electrical activity, which they believe contributed to the organoids' longevity.
The research addresses a major limitation in previous organoid models, which typically only mimicked early brain development over a period of months and showed significant variability between batches. "The unprecedented longevity and lifelike qualities of these tissue models could afford us the opportunity to dig deeper into how conditions such as autism emerge and unfold later in life," said Andrea Beckel-Mitchener, acting director of NIH's National Institute of Mental Health.
When researchers transferred neurons from older to younger organoids, the older cells continued progressing as they had in their previous environment, skipping developmental steps compared to younger neighboring cells. This indicated the organoid cells possessed an intrinsic developmental clock reflecting mechanisms of natural human brain development, the researchers said.