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Physical Properties of Productive Stem Cells Identified

Eric Darling (Brown University)

Eric Darling (Brown University)

Biomedical engineers at Brown University in Providence have identified the physical properties of adult stem cells that indicate their most productive use in engineering new tissue. The findings of the team led by biomedical engineering professor Eric Darling (pictured left) appear online in the journal Proceedings of the National Academy of Sciences; paid subscription required.

Darling’s research team shows that physical properties, such as stiffness and viscosity, of adult mesenchymal stem cells derived from fat can predict whether they will turn into bone, cartilage, or fat. Liposuction waste could be a source of those stem cells. Adult mesenchymal stem cells have the ability to differentiate into multiple types of cells in the body.

The researchers cloned adult human stem cells derived from adipose (body fat) into 32 stem cell populations. They then use an atomic force microscope — a device that can scan with very high resolutions — to measure the cells’ size, ability to withstand pressure, and changes in inter-cellular forces over time.

After taking those measurements, Darling’s team chemically induced the stem cell groups to differentiate, and the researchers analyzed the metabolites the cells produced as they matured over the next few weeks. For each group of stem cells, the metabolites indicated the relative proportion that differentiated into one form of tissue or another.

The Brown team could then correlate the two sets of data — the physical properties of the stem cells based on the earlier measurements, and the tissue types into which the stem cells differentiated. The correlations revealed:

– The stiffest cell populations produced more bone.
– The cells with the highest viscosity were more likely to become cartilage.
– The softest cells were likely to produce the most fat.

The researchers then simulated a sorting exercise to determine if filtering a sample by different mechanical properties could result in extracting a higher concentration of useful cells from tissue. The team found that current molecular biomarker methods yield less than 1 percent in useful cells, while using mechanical properties could increase those yields to 3 percent for bone-making cells, 6 percent for cartilage, and 9 percent for fat.

While Darling’s research provided an early proof of concept for connecting physical properties of stem cells to their most likely tissue outputs, the technology still needs to be made practical for day-to-day use by clinicians. “To actually apply this, we need some sort of high-throughput mechanical testing device,” says Darling. “That’s something that my lab is working on right now.”

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