ARLINGTON, Va., May 18, 2004 -- Researchers have discovered a potentially powerful tool for controlling whether bone marrow stem cells grow into skin, fat, bone, or other cell types.

The research offers another handle that might be used to control stem cells with the long-term goal of regenerating or repairing damaged tissue.

"Shape is critical to the stem cells' differentiation," said Whitaker investigator Christopher Chen, M.D., Ph.D., of Johns Hopkins University. "It can actually induce molecular signals known to encourage fat cell or bone cell development."

Chen and colleagues reported in the April issue of Developmental Cell that bone marrow stem cells forced into spherical shapes would become fat cells, while those allowed to stretch and flatten became bone cells.

The group worked with a type of marrow cells called mesenchymal stem cells, which naturally differentiate into fat cells, cartilage, bone cells, cardiac cells or smooth muscle cells.

"The types of cells that come from mesenchymal stem cells all have shapes specific to their functions," Chen said. "We wondered whether the stem cells' shapes could actually direct their differentiation."

Applying micropatterning techniques similar to those used in microelectronics, Chen's group etched microscopic patterns of squares onto rubber stamps and seeded these with with a protein (fibronectin) that attracts cells.

The stamp transferred the pattern to a flat surface, depositing the clumps of fibronectin into small islands to which cells can stick. The size of the island determines whether cells will collect into balls or spread out. Stem cells attracted to small islands balled up and began to become fat cells, while those on the large islands stretched out and began to form bone. The medium-sized islands induced the growth of both cell types.

"With this tool we can restrict the ability of individual cells to spread, and we can do so with thousands of cells at a time," Chen said.

After seven days of growth, 45 percent of the cells forced to ball-up started to become fat and half of the spread-out cells started turning into bone. After four weeks, all of the spherical cells had become fat cells and all of the oblong cells had turned to bone. Other molecular signals were introduced into the experiment, but they did not overcome those generated by the shapes of the cells.

In follow-up experiments, the group plans to investigate the molecular mechanisms by which shape influences cell fate.

Chen's group included Rowena McBeath, Dana Pirone, Celeste Nelson and Kiran Bhadriraju, all of Johns Hopkins. Support came from the National Institute of General Medical Sciences, the National Institutes of Health's Medical Scientist Training Program, the Ruth L. Kirschstein National Research Service Award, and The Whitaker Foundation.

Contact:
Christopher Chen, Johns Hopkins University
Frank Blanchard, The Whitaker Foundation