Thick, dense nanofibrous sheets can prevent brain cancer metastasis by trapping cells and stopping migration processes.
Cells often migrate in response to specific external signals including chemical and mechanical signals. During wound healing, cell migration occurs when new cells migrate to the site of injury to replace damaged cells. However, cell migration also plays a vital role in metastasis as it facilitates the transport and spread of cancer cells within the body. For instance, glioblastoma multiforme, a highly invasive brain tumour, spreads via migration of the tumour cells. When tumour cells spread and grow abnormally fast, this can render conventional tumour removal methods ineffective.
To improve the safety and effectiveness of therapeutic strategies, scientists have sought to improve their understanding of tumour invasion mechanisms and since strategised to capture migrating tumour cells. By engineering similar structures of desired geometries, experts believe that it may be possible to gain control over cell migration as the process is dictated by the structure and orientation of the extracellular matrix.
Now, researchers from the University of Fukui have designed a nanofibre-based platform that resembles the extracellular matrix in hopes of halting the spread of cancerous cells, specifically glioblastoma multiforme cells.
“We fabricated a nanofibrous sheet in which the fibre density changes from end to end gradually using a technique called ‘electrospinning’ and carried out a culture,” said Dr. Satoshi Fujita, who headed the study.
The researchers compared cell movement in nanofibres of different densities and observed notable differences. While denser fibres increased the formation of focal adhesion clusters in the cells thereby leading to slower migration, low-density fibres produced the opposite effect. Taking note of this negative relationship between cell movement and fibre density, the researchers then designed a nanofibrous sheet with stepwise varying densities to control and direct the migration of cells.
By arranging the fibres in a high-to-low density configuration, they effectively restricted the movement of cells as the gaps between the zones prevented cell migration, resulting in cells being trapped in the high-density zones. This one-way migration was observed for the first time and the researchers named it “cell trapping” after fish and insect traps that cause their prey to travel along a single direction before trapping it. Accordingly, a low-to-high configuration encouraged migration.
“The study demonstrates the feasibility of capturing migrating cells using electrospun nanofibres that mimic the microenvironment of the brain,” commented Dr. Fujita. With these remarkable findings, the team is hopeful about the potential of their nanofibre-based platform.
“It is available for the design of scaffolding materials, which are the basis of regenerative medicine, in combination with various fibre processing technologies and material surface treatment technologies. This could lead to the development of practical applications of regenerative medicines,” speculated Dr. Fujita, “In addition, it can be used as a processing technology for culture carriers for efficient production of biological drugs including proteins, antibodies, and vaccines.” [APBN]
Source: Huang et al. (2021). Cell Trapping via Migratory Inhibition within Density-Tuned Electrospun Nanofibers. ACS Applied Bio Materials, 4(10), 7456-7466.