Neural stem cells help maintain their microenvironment – ScienceDaily

Researchers from Tokyo Medical and Dental University (TMDU) have shed new light on the characteristics of the niche in which neural stem cells reside in the developing brain.

TOKYO, Japan — When it comes to cell types, stem cells have unlimited potential — literally. These self-renewing cells, capable of creating any type of cell in the body, live in specialized microenvironments known as niches. Now, researchers in Japan have shed new insight into the dynamics of the neural stem cell niche, the home of stem cells in the brain.

In a new study published in Inflammation and regenerationresearchers from Tokyo Medical and Dental University (TMDU) investigated the effects of hypoxic conditions (low oxygen) on the status of neural stem cells during development.

Neuronal stem and progenitor cells (NPSCs) give rise to cells of the brain and nervous system. NSPCs are known to live in an anoxic niche, which means that the oxygen levels in the niche are lower than those in the surrounding tissues. However, the formation of this niche, and how NSPCs maintain themselves within it, is not entirely clear. The TMDU-led research team set out to investigate the effects of hypoxic conditions within the neural stem cell niche using a cell culture model of NSPCs isolated from the anterior progenitors of embryonic mice. They cultured these cells in neurospheres, or clusters of free floating stem cells, under conditions of low oxygen and normal oxygen.

“The results were striking, as a significant increase in neurosphere formation was observed under conditions of hypoxia compared to normal conditions for anoxia,” says Taichi Kashiwagi, co-lead author of the study. “This led us to explore the factors that play a role in the maintenance and proliferation of NSPCs under hypoxic conditions.”

The researchers evaluated a protein called vascular endothelial growth factor A (VEGF-A) as a potential candidate. When the research team added VEGF-A to NSPC cultures, neurosphere formation increased dramatically. Conversely, blocking VEGF-A with a pharmacological inhibitor reduced the increase in neurosphere formation under conditions of low oxygen. In addition, VEGF-A expression was found to be upregulated in NSPCs under low anoxic conditions.

“We found that NSPCs treated with VEGF-A showed lower rates of cell death and increased cell proliferation,” says senior author Tetsuya Taga. “VEGF-A is a factor that appears to contribute to NSPC maintenance under hypoxic conditions.”

These results indicate that NSPCs help maintain their population by releasing VEGF-A under hypoxic conditions. While other factors may also contribute to NSPC maintenance, these findings shed new light on neural stem cell niche formation during development, and may serve as a basis for further studies on hypoxic niche autoregulation.

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