Stem cells may restore function to diseased organs.
By piercing liver cells with rapid pulses of electricity, scientists at UC San Francisco have demonstrated an entirely new way to transplant cells into organs to treat disease.

Because the technique provides a hospitable environment for newly introduced cells, it may dramatically boost survival of stem cells transplanted to restore a failing liver, heart or lungs, and may one day ease the critical shortage of donor organs, the researchers said.

Findings from a mouse study appeared in the journal BioTechniques, published May 15.

Success of stem cell treatments largely depends on how well the new cells survive and proliferate in the target region. But the authors said that establishing a thriving population of new cells in host organs remains difficult.

“Our research is in its early stage,” said Tammy T. Chang, MD, PhD, assistant professor in the UCSF Department of Surgery and the paper’s lead author. “We’ve shown we can create the hospitable environment for new cells. Full demonstration of the procedure’s value will be when we can introduce stem cells to restore function to diseased livers and other organs.”

A major barrier to efficient cell transplantation has been the failure to provide space for new cells to take hold inside a diseased host organ such as a liver, Chang said noting that non–functional cells block newly transplanted cells from becoming established. Chang has led the effort to develop and test the new procedure that first clears away host cells to make room for transplanted cells.

The new surgical approach uses a technique called irreversible electroporation, or IRE, to kill a section of liver cells with microsecond electric pulses, creating a pocket for transplanting new cells into the organ with little collateral damage.

Chang directed IRE at selected sites on the liver of anesthetized mice to prepare for transplanting cells into the organs. The electric pulses sculpted out the needed pocket without harming vital structures between cells called the extracellular matrix, which provides support critical for the new cells to survive. The IRE procedure triggers only minimal inflammation and scarring in treated tissues, a major reason why new cells can become established.

“Inflammation normally produces scar tissue as part of the healing process, and this environment is hostile to new cells,” Chang said. “We found that at certain settings, IRE can kill organ cells without inducing inflammation, leaving behind an environment – a niche – friendly for new cells to set up shop. We believe that establishing this niche is essential for new cells to engraft efficiently.”

After using IRE to create the hospitable niche in the mouse livers, Chang transplanted clusters of liver cells, or hepatocytes, into the space. The hepatocytes established healthy colonies, still present two weeks later.

The IRE pre–treatment improved engraftment of transplanted cells compared to no IRE treatment, Chang found.

Fully developed, the technique could be used as a minimally invasive stem cell transplantation procedure to regenerate organs compromised by defects in specific types of cells, such as in end–stage liver, kidney, heart and lung diseases.