Research shows meninges contain neural progenitor stem cells

In a cross-domain study directed by professor Peter Carmeliet, researchers discovered unexpected cells in the protective membranes that enclose the brain, the so-called meninges. These ‘neural progenitors’ – or stem cells that differentiate into different kinds of neurons – are produced during embryonic development. These findings show that the neural progenitors found in the meninges produce new neurons after birth – highlighting the importance of meningeal tissue as well as these cells’ potential in the development of new therapies for brain damage or neurodegeneration. A paper highlighting the results was published in the leading scientific journal Cell Stem Cell.

Before the discoveries of the last few decades, neurologists once thought that the brain became ‘static’ after childhood. This dogma has changed, with researchers finding more and more evidence that the brain is capable of healing and regenerating in adulthood, thanks to the presence of stem cells. However, neuronal stem cells were generally believed to only reside within the brain tissue, not in the membranes surrounding it.

Believed in the past to serve a mainly protective function to dampen mechanical shocks, the meninges have been historically underappreciated by science as having neurological importance in its own right. The data gathered by the team challenges the current idea that neural precursors – or stem cells that give rise to neurons – can only be found inside actual brain tissue.

Prof. Peter Carmeliet said “The neuronal stems cells that we discovered inside the meninges differentiate to full neurons, electrically-active and functionally integrated into the neuronal circuit. To show that the stem cells reside in the meninges, we used the extremely powerful single-cell RNA sequencing technique, a very novel top-notch technique, capable of identifying the (complex gene expression signature) nature of individual cells in a previously unsurpassed manner, a première at VIB.”

 When it comes to future leads for this discovery, the scientists also see possibilities for translation into clinical application, though future work is required. Prof. Peter Carmeliet said “An intriguing question is whether these neuronal stem cells in the meninges could lead to better therapies for brain damage or neurodegeneration. However, answering this question would require a better understanding of the molecular mechanisms that regulate the differentiation of these stem cells. How are these meningeal stem cells activated to become different kinds of neurons? Can we therapeutically ‘hijack’ their regeneration potential to restore dying neurons in, for example, Alzheimer’ Disease, Parkinson’s Disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders? Also, can we isolate these neurogenic progenitors from the meninges at birth and use them for later transplantation? These findings open up very exciting research opportunities for the future.”

 Moving into unchartered territory is high risk, and can offer high gain, but securing funding for such type of research is challenging. However, Carmeliet’s discoveries were made possible to a large extent by funding through “Opening the Future: pioneering without boundaries”, a recently created Mecenas Funding Campaign for funding of high-risk brain research but with potential for breakthrough discoveries, started up by the KU Leuven in 2013 and unique in Flanders.

Citation: “Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex”. Francesco Bifari1, Ilaria Decimo1, Annachiara Pino, Enric Llorens-Bobadilla, Sheng Zhao, Christian Lange, Gabriella Panuccio, Bram Boeckx, Bernard Thienpont, Stefan Vinckier, Sabine Wyns, Ann Bouché, Diether Lambrechts, Michele Giugliano, Mieke Dewerchin, Ana Martin-Villalba, Peter Carmeliet. Cell Stem Cell 2016.
DOI: http://dx.doi.org/10.1016/j.stem.2016.10.020
Research funding: Mecenas funding initiative by the KU Leuven
Adapted from press release by VIB Vlaams Instituut Voor Biotechnologie (The Flaunders institute of biotechnology)