Monday, October 21, 2013

Grooved surface increases the yeild of iPS cells

Pluripotent stem cells, created from human skin or mouse ear tissue, are shown here becoming endoderm cell. The endoderm is one of the three primary germ layers that ultimately contribute to the development of vital organs (liver, pancreas, etc.). The yellow highlights the Sox17 protein, expressed during endoderm development. Cell nuclei are shown in magenta. (Image courtesy of Song Li's Lab)
Back in 2012 Shinya Yamanaka got a Nobel Prize for his discovery that it's possible to revert cells from mature tissues into a stem cell state. (These cells are known as iPS cells.) We now have a number of grantees who are harnessing this discovering to develop therapies for diseases, and the cells turn out to be a great tool for understanding how diseases develop and testing drugs.

But really, that discovery was just the beginning. Since Yamanaka's announcement back in 2006, scientists have been trying to find better ways of generating iPS cells. They are trying to make the process more efficient and also safer. A concern has been that the original technique relied on inserting genes into the cells that might make them unsafe for transplantation.

One of our grantees at University of California Berkeley has found that the cells' physical environment can help prompt their conversation. Song Li has a Basic Biology award from CIRM to develop better ways of generating iPS cells and then use those to find therapies for neurological diseases.

When the group placed skin cells on a surface with tiny parallel grooves then applied the usual cocktail of molecules to induce their reprogramming, they got four times the usual number of iPS cells. They tried the same thing growing the cells on parallel nanofibers with the same effect.

They quote Li in a press release about the work, which was published October 20 in Nature Materials:
“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.”
The lead author on the paper, Timothy Downing, said the technique might be effective because it causes the cells to elongate like they would in the body:
“Cells elongate, for example, as they migrate throughout the body. 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 work is an example of how basic research can help improve the work of teams developing new therapies. If our grantees develop a more efficient and safer way of generating iPS cells, then the scientists already down the path of developing new therapies will have access to more and safer cells to use in their work.

Amy Adams

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