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Crowding stem cells' personal space directs their future

Johns Hopkins scientists report that restricting the shape and personal space of human stem cells from bone marrow is more important than any known molecular signal in determining the cell type they become.

Understanding the signals that tell stem cells what type of cell to become, and then harnessing those cues to get a single desired cell type, is key to any effort to use these or more primitive embryonic stem cells to regenerate or repair damaged tissue.

In the April issue of Developmental Cell, the Hopkins researchers report that mesenchymal (pronounced mez-EHN-kih-mal) stem cells forced to be spherical efficiently transform into precursors to fat cells, while those allowed to stretch and flatten move closer to becoming bone cells. These stem cells can naturally become fat cells, cartilage, bone cells, or smooth, cardiac or skeletal muscle.

"The types of cells that come from mesenchymal stem cells all have shapes specific to their functions, so we wondered whether the stem cells' shapes could actually direct their differentiation," says Christopher Chen, M.D., Ph.D., an assistant professor of biomedical engineering at Johns Hopkins. "The answer is that shape is critical to the stem cells' differentiation. It can actually induce molecular signals known to encourage fat cell or bone cell development and causes complete, uniform differentiation."

In the first week of laboratory studies, about 45 percent of stem cells forced to be round moved toward fat cell development, and 50 percent of spread-out cells got closer to being bone cells. By four weeks, all cells had followed the path dictated by their shape, Chen says, making shape the most powerful factor in whether human mesenchymal stem cells become fat or bone in the lab.

Ever since these stem cells were first isolated in the late 1990s, scientists have recognized that which cell type they become depends on the density at which they are grown in the lab. But while sparse
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
16-Apr-2004


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