Nano-scale patterns induce stem cell differentiation

Soon after fertilization, the early embryo – or blastula – consists of a ball of identical cells which have the ability to differentiate into every cell type of which the adult organism consists.

The human body, for example, contains at least three hundred different cell types. An embryonic stem cell can, in theory, become any one of those cell types, differentiates into one type of cell or another according to an intricate cascade of genetic signals received from its environment.

In recent years, researchers have elucidated some of the signals which induce stem cells to differentiate along a particular path. This has enabled them to influence stem cell differentiation under laboratory conditions. By adding the appropriate signal, stem cells can be made to grow into blood cells, nerve cells or bone cells.

A team led by Matthew Dalby at Glasgow University’s Centre for Cell Engineering now reports that it has induced stem cells to differentiate into bone cells, not by adding chemicals to them, but by growing them on a surface with a nano-scale pattern etched onto it.

Dalby and his team used a technique called electron beam lithography, which is used to design microchips, to etch a microscopic pattern on the substrate to which the stem cells were attached.

E-beam lithography allowed the Glasgow team to make surfaces covered with 100 nanometre-wide and 150 nanometre deep pits. By altering the substrate topography in this way, they succeeded in causing the stem cells to differentiate into bone cells instead of muscle or cartilage cells.

“We’re not using any other external factors to induce differentiation. The topography is enough,” says Dalby. It was found that cells grown on a flat surface remained undifferentiated, as did cells grown on a surface of highly-ordered nano-pits. However, when stem cells were grown on a surface that was partly random and partly uniformly patterned, they differentiated into bone cells which then underwent calcification, or impregnation with calcium which causes hardening and bone formation.

It is as yet unclear how substrate topography affects stem cell differentiation. The patterning could be providing the cells with cues similar to those they would normally receive from their surroundings.

The work may lead to the discovery of surfaces which can induce stem cells to differentiate into other cell types . It may also lead to improved implants. Existing bone and hip implants are eventually coated with soft tissues which impairs their functioning. Nano-engineering could in the future be used to bring about differentiation of implanted cells into bone cells while preventing soft tissue formation.