Bioengineers at the
Pluripotent stem cells, created from human skin or mouse ear tissue, are shown here developing into neurons. Cell nuclei are shown in blue, and the red highlights a type of filament protein expressed in nerve cells. (Image courtesy of
The researchers grew fibroblasts - cells taken from human skin and mouse ears - on surfaces with parallel grooves measuring 10 micrometers wide and 3 micrometers high. After two weeks of culture in a special cocktail used to reprogram mature cells, the researchers found a four-fold increase in the number of cells that reverted back to an embryonic-like state compared with cells grown on a flat surface. Growing cells in scaffolds of nanofibers aligned in parallel had similar effects.
The study, published online today (
The 2012 Nobel Prize in Physiology or Medicine was awarded to scientists who discovered that it was possible to reprogram cells using biochemical compounds and proteins that regulate gene expression. These induced pluripotent stem cells have since become a research mainstay in regenerative medicine, disease modeling and drug screening.
"Our study demonstrates for the first time that the physical features of biomaterials can replace some of these biochemical factors and regulate the memory of a cell's identity," said study principal investigator
The current process for reprogramming cells relies on a formula that uses a virus to introduce gene-altering proteins into mature cells. Certain chemical compounds, including valproic acid, that can dramatically affect global DNA structure and expression are also used to boost the efficiency of the reprogramming process.
Stem cells created by
"The concern with current methods is the low efficiency at which cells actually reprogram and the unpredictable long-term effects of certain imposed genetic or chemical manipulations," said study lead author
Previous studies have shown that physical and mechanical forces can influence cell fate, but the effect on epigenetic state and cell reprogramming had not been clear.
The new study found that culturing cells on micro-grooved biomaterials improved the quality and consistency of the reprogramming process, and was just as effective as valproic acid.
"Cells elongate, for example, as they migrate throughout the body," said Downing, who is now a research scientist in Li's lab. "In the case of topography, where we control the elongation of a cell by controlling the physical microenvironment, we are able to more closely mimic what a cell would experience in its native physiological environment. In this regard, these physical cues are less invasive and artificial to the cell and therefore less likely to cause unintended side effects."
The researchers are studying whether growing cells on grooved surfaces could eventually replace valproic acid and perhaps other chemical compounds in the reprogramming process.
"We are also studying whether biophysical factors could help reprogram cells into specific cell types, such as neurons," said
Funding from the
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