Control Knobs for Stem Cells Identified

by Hannah Punitha on Dec 5 2008 5:12 PM

By discovering that voltage changes across the membrane of adult human stem cells can control their differentiation, scientists have found what they call as 'control knobs' for such cells.

The 'control knobs' in turn can help scientists to manipulate the behaviour of adult stem cells. Tufts doctoral student Sarah Sundelacruz, Professor of Biology Michael Levin, and Chair of Biomedical Engineering David L. Kaplan (corresponding author), the study proved that electrophysiology also plays a key role in stem cell biology

For the study, the researchers examined the changes in membrane potential (voltage across the membrane) shown by human mesenchymal stem cells (hMSCs) obtained from donor bone marrow as the hMSCs were differentiating into fat and bone cells.

They found that hyperpolarization (increased difference between the voltage in the interior and exterior of a cell) was characteristic of differentiated cells compared with undifferentiated cells and that hMSCs show different membrane potential profiles during bone vs. fat differentiation.

"We have found that voltage changes act as a signal to delay or accelerate the decision of a stem cell to drop out of a stem state and differentiate into a specific cell type. This discovery gives scientists in regenerative medicine a new set of control knobs to use in ongoing efforts to shape the behavior of adult stem cells," said Levin.

He added: "In addition, by uncovering a new mechanism by which these cells are controlled in the human body, this research suggests potential future diagnostic applications."

In order to find out if hyperpolarization was functionally required for differentiation, the scientists depolarized the hMSCs by exposing them either to high levels of extracellular potassium ions or to ouabain, a compound that blocks the transfer of ions in and out of cells.

Both treatments disrupted the normal increase in negative voltage that occurs during differentiation and suppressed fat and bone cell differentiation markers.

In the other hand, treatment with hyperpolarizing reagents up-regulated bone cell markers, which indicated that voltage changes are not merely permissive for differentiation but can act as an instructive signal to either induce or inhibit differentiation.

The researchers said that more research was to be done to find out whether hyperpolarization also determines which specific type of cell stem cells will differentiate into.

The study, titled "Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells," was published in a recent issue of PLoS ONE.