Scientists grow brain tissue using electrically charged hydrogel

A promising step toward developing therapies based on brain tissue regeneration.
Mert Erdemir
The semitransparent hydrogel used in this study.
The semitransparent hydrogel used in this study.

Satoshi Tanikawa, et al. 

A team of researchers from Hokkaido University has successfully grown new brain tissue using electrically charged hydrogel materials and neural stem cells. This is a significant development since the tissue in our brain doesn't regenerate after being damaged compared to other parts of the body, such as the skin. Therefore, this new approach could pave the way for future treatments for brain damage.

The hydrogel offers optimal adhesion for cells

Researchers first developed a hydrogel material that could maintain the survival of neural stem cells. Then they found that a neutral hydrogel comprising an equal amount of positively and negatively charged monomers offered the best cell adhesion.

To achieve brain tissue stiffness, the scientists adjusted the crosslinker molecule ratios. Following this, they developed pores in the gel that could serve as a suitable environment for cell culture.

"When I saw the 3D structure of the porous hydrogels that my colleague Tomáš showed in a meeting, I thought they could be utilized in regenerative treatments as a scaffold for growing nerve cells," said lead author Satoshi Tanikawa in an institutional press release.

As the next step, the gel was soaked in a growth factor serum to boost blood vessel growth. After that, it was implanted in damaged areas of mouse brains. Three weeks later, researchers observed that cells and neuronal cells from the surrounding host brain tissue had entered the hydrogel. Additionally, blood vessels had also grown.

Subsequently, the researchers introduced neural stem cells into the hydrogel. After a period of 40 days, the team noted a high survival rate among the stem cells, with some having differentiated into neuronal and neuron-maintaining astrocyte cells.

The hydrogel also showed a degree of integration with the host brain tissue as host cells infiltrated the hydrogel. In contrast, some new neuronal cells migrated from the hydrogel to the surrounding brain tissue.

Following a stepwise approach

The stepwise approach was critical for the process since implanting the hydrogel and transplanting neural stem cells simultaneously proved ineffective.

The study is significant for developing therapies based on brain tissue regeneration. The next steps entail determining the optimal timing for transplantation and assessing the impact of the inflammatory response on transplanted cells.

"Conditions affecting blood vessels in the brain, such as cerebral infarction, are a major disease," said Tanikawa. "They not only have a high mortality rate, but those that survive struggle with severe after-effects. I think this research will become the foundation for medical treatments that could help such patients."

The results of the study were published in Scientific Reports on February 14.

Study abstract:

Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation towards glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.

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