Human Glial Cells Can Be Reprogrammed

For the first time the formation of new nerve cells from somatic cells of the human brain has succeeded: Specific cells of the adult human cerebral cortex could be reprogrammed into functioning neurons with the aid of two transcription factors.

The regeneration of functional neurons is an innovative approach to the therapy of neurodegen­erative diseases such as Alzheimer’s disease or stroke. In the adult mammalian brain, however, most areas no longer contain neuronal stem cells or progenitor cells from which new neurons could be formed.

Several years ago, members of the Institute of Stem Cell Research headed by Magdalena Götz showed in a mouse model that by selective transfer of individual transcription factors it is possible to reprogram glial cells – i.e. supporting cells with multiple functions – to nerve cells. Transcription factors are regulatory proteins that control which genes are active or inactive in the cells.

Now a research team led by Magdalena Götz and Benedikt Berninger has succeeded in proving that the animal experimental approach is also applicable to human glial cells. Using specimens derived from the surgery of adult epilepsy patients, Marisa Karow and her colleagues showed that specific cells of the cerebral cortex (cells derived from pericytes) can be reprogrammed into neurons through the retrovirus-mediated expression of the two transcription factors Sox2 and Mash1. These induced neurons fire action potentials and form networks with other neurons; thus, they are able to integrate themselves into neuronal networks.

This shows for the first time that there are cells in the adult brain which can be directly reprogrammed into functional neurons for therapy purposes – without having to take a detour via pluripotent cells. On the basis of this knowledge, researchers are seeking active agents to activate the reprogramming of glial cells in patients with neurodegenerative diseases or brain traumas and thus to initiate a self-healing process in the injured areas of the brain.

The brain consists of two main types of cells: the neurons, which transmit information, and the glial cells, which have a supporting function and are involved in the metabolism of the brain. In many degenerative diseases of the brain – stroke, Alzheimer’s disease, Parkinson’s disease – the neurons are primarily damaged.