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Biological Chemistry

Bedding Down Stem Cells

Chemical Biology: Fully synthetic structure supports growth of human pluripotent stem cells

by Sarah Everts
November 22, 2010 | A version of this story appeared in Volume 88, Issue 47

The different cells shown have come from differentiation of stem cells grown on the new bed. (Same scale for all images.)
Credit: Joseph R. Klim

Finding a chemically defined diet and environment that keeps human stem cells in their omnipotent state has been challenging because the cells have such picky tastes. Now, researchers led by biochemist Laura L. Kiessling at the University of Wisconsin, Madison, have developed a new chemically defined bed on which to grow these promising cells (Nat. Methods, DOI: 10.1038/nmeth.1532). The work adds to the toolbox of chemically defined culturing techniques that many researchers believe will be essential to gain regulatory approval of stem cell therapies.

Researchers typically grow pluripotent stem cells, which are stem cells that can differentiate into a multitude of cell types, on an undefined mixture of proteins and sugars called Matrigel, which is produced from a tumor cell line. Because of Matrigel’s provenance, “any stem cell that touches the stuff could never be used for human therapies,” comments Shuguang Zhang, a biomedical engineer at MIT.

Growing pluripotent stems cells on chemically defined media and chemically defined beds would solve this problem. But when grown under such conditions, pluripotent stem cells have frustrated researchers by rapidly differentiating. Pluripotent stem cells “are like babies. It’s hard to stop them from growing and learning,” Zhang adds.

Kiessling’s approach is to grow the stem cells on a bed of either alkanethiol self-assembling monolayers or streptavidin proteins that are decorated with specific sequences of peptides. Her team screened some 500 different combinations of peptides chosen from a selection of proteins typically found in vivo around the cells. They found that stem cells grew best on the monolayers that present two particular peptides: one called RGD for arginine-glycine-aspartic acid and a novel sequence from the protein heparin. The new bed supports eight different pluripotent stem cell lines for two to three months, which is comparable with Matrigel, Kiessling says. Her team checked that these pluripotent cells could be induced to differentiate normally into specialized cells.

This year, several other groups have also reported beds made from sulfopropyl polymers and peptide-acrylates that support stem cell growth in completely chemically defined conditions (Nat. Biotech., DOI: 10.1038/nbt.1629 and 10.1038/nbt.1631).

All of these chemically defined beds are promising, notes Larry A. Couture, a stem cell researcher at the Beckman Research Institute, but Kiessling’s work characterizes her stem cell scaffold across a greater number of stem cell lines. It also “provides additional clues to unravel the growth requirements of these cells and will very likely influence other groups that are trying to sort this out,” he says. Couture adds that more extensive peptide and chemical screening work could lead to improved beds for stem cells.



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