News release

From: Springer Nature

Neuroscience: Long-lived human brain organoids record the passage of timeBrain organoids (3D brain-like tissue formed from laboratory-grown human cells) exhibit molecular signatures of their developmental age, according to a paper published in Nature. The organoids — observed over five years, the longest period reported to date — successfully matured and developed traits resembling those of postnatal brains, offering key insights into later-stage brain cell development.

The human brain takes around two decades to fully mature. Brain organoids may facilitate research into postnatal brain development, but current studies largely mimic early phases and in most studies last for just months, with low rates of long-term survival and early loss of vulnerable cells such as neurons. Successfully culturing complex tissue with many different types of brain cells over years in the lab may enable a more accurate representation of mature brains and their development.

Paola Arlotta and colleagues cultured human brain organoids for more than five years. The authors created ‘chimeric organoids’ by mixing specialised biological brain cells of different ages, both younger and more mature. Subsequently, older progenitor cells bypassed earlier stages of development and produced mature neuron types (which would usually take two months to form) in just two weeks. This indicates that the cells recorded markers of both age and the time spent developing. Overall, whole-genome profiling of long-cultured organoids revealed traits resembling those in late-prenatal and postnatal human brains. As the organoids aged, they eventually acquired more mature gene expression patterns, neuronal types, and spine structures.

These long-lived organoids, which accurately retain characteristics associated with both developmental age and time spent in culture, present future research opportunities for the study of mature brain cells, the authors conclude.