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New 'control knobs' for stem cells identified
December 04, 2008Tufts study shows that changes in membrane voltage control timing of differentiation in adult stem cells
MEDFORD/SOMERVILLE, Mass. - Natural changes in voltage that occur across the membrane of adult human stem cells are a powerful controlling factor in the process by which these stem cells differentiate, according to research published by Tufts University scientists.
Tufts doctoral student Sarah Sundelacruz, Professor of Biology Michael Levin, and Chair of Biomedical Engineering David L. Kaplan (corresponding author) published their paper "Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells" in the November 17, 2008, issue of PLoS ONE (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003737).
"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. "In addition, by uncovering a new mechanism by which these cells are controlled in the human body, this research suggests potential future diagnostic applications."
Harnessing the potential of stem cells for applications such as wound healing and tissue regeneration is a tantalizing yet daunting task. Although many studies indicate that electrophysiology plays a crucial role in cell proliferation and differentiation, its functional role in stem cell biology is poorly understood.
The Tufts researchers studied 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.
To determine whether 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 contrast, treatment with hyperpolarizing reagents up-regulated bone cell markers - indicating that voltage changes are not merely permissive for differentiation but can act as an instructive signal to either induce or inhibit differentiation.
More study is needed to determine whether hyperpolarization also determines which specific type of cell stem cells will differentiate into, according to the Tufts researchers.
Tufts University
"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. "In addition, by uncovering a new mechanism by which these cells are controlled in the human body, this research suggests potential future diagnostic applications."
Harnessing the potential of stem cells for applications such as wound healing and tissue regeneration is a tantalizing yet daunting task. Although many studies indicate that electrophysiology plays a crucial role in cell proliferation and differentiation, its functional role in stem cell biology is poorly understood.
The Tufts researchers studied 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.
To determine whether 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 contrast, treatment with hyperpolarizing reagents up-regulated bone cell markers - indicating that voltage changes are not merely permissive for differentiation but can act as an instructive signal to either induce or inhibit differentiation.
More study is needed to determine whether hyperpolarization also determines which specific type of cell stem cells will differentiate into, according to the Tufts researchers.
Tufts University
Stem Cells Current Events and Stem Cells News RSSNew discovery about the formation of new brain cells
The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Umbilical cord blood stem cell transplant may help lung, heart disorders
Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
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