Study: Neural stem cells support the maintenance of their microenvironment

The potential of stem cells is practically unbounded when compared to other cell types. These self-renewing cells reside in niches, which are specialized micro-environments and may give rise to every type of cell in the body. The dynamics of the neural stem cell niche, the brain’s home for stem cells, have recently received new insight from Japanese researchers.

In a new study published in Inflammation and Regeneration, researchers from Tokyo Medical and Dental University (TMDU) investigated the effects of hypoxic (low oxygen) conditions on the brain stem cell niche during development. The brain and nervous system’s cells are derived from neural stem and progenitor cells (NPSCs). It is well known that NSPCs live in a hypoxic niche, which means that its oxygen content is lower than that of the tissues around it. It is not totally clear how NSPCs maintain their place within this niche . The TMDU-led research team used a cell culture model of NSPCs obtained from the forebrains of embryonic mice to explore the consequences of low oxygen conditions within the neural stem cell niche.

In low-oxygen and high-oxygen conditions, they grew these cells into neurospheres, or free-floating stem cell clusters.
The co-lead author of the study, Taichi Kashiwagi, notes that the findings were “shocking,” with considerably more neurosphere production being seen under hypoxia settings as compared to normoxic ones. This prompted us to investigate the variables that influence the survival and growth of NSPCs in hypoxic environments.

Vascular endothelial growth factor-A (VEGF-A) was considered by the researchers as a viable contender. The amount of neurospheres that formed in the NSPC cultures was dramatically boosted when they  added VEGF-A. On the other hand, the rise in neurosphere formation under low oxygen conditions was reduced by blocking VEGF-A with a drug inhibitor. Moreover, it was discovered that low oxygen levels increased the expression of VEGF-A in NSPCs.

Tetsuya Taga, senior author, reports that they discovered that NSPCs treated with VEGF-A displayed decreased rates of cell death and increased cell proliferation. In low oxygen environments, VEGF-A is a factor that “appears to contribute to NSPC maintenance.”
These results suggest that in hypoxic conditions, NSPCs generate VEGF-A that contributes to the maintenance of their own population. These findings provide new insight into the composition of the neural stem cell niche during development and may lay the groundwork for future research on the self-organization of the hypoxic niche, even though other factors may also play a role in NSPC maintenance.