Researchers are first to use common virus to 'fortify' adult stem cells

(Press-News.org) WINSTON-SALEM, N.C. – April 1, 2013 – Using the same strategy that a common virus employs to evade the human immune system, researchers at Wake Forest Baptist Medical Center's Institute for Regenerative Medicine have modified adult stem cells to increase their survival – with the goal of giving the cells time to exert their natural healing abilities.

"Basically, we've helped the cells be 'invisible' to the body's natural killer cells, T cells and other aspects of the immune system, so they can survive to promote healing," said Graca Almeida-Porada, M.D., Ph.D., senior author and professor of regenerative medicine at Wake Forest Baptist.

The research, reported in the current issue of PLOS One, a peer-reviewed, open access journal, involves mesenchymal stem cells (MSCs), found in bone marrow, peripheral and cord blood and fetal liver and lung tissue. These cells are known for their ability to migrate to damaged tissues and contribute to healing. However, like all cells, they are susceptible to being killed by the body's complement system, a part of the immune system involved in inflammation and organ rejection.

"These cells have a natural ability to help modulate the immune response, so if we can increase their survival, they theoretically could be a therapy to decrease inflammation and help transplant patients avoid organ rejection," said Almeida-Porada.

In the study, the researchers evaluated the potential of human cytomegalovirus (HCMV), a member of the herpes virus family, to help increase the survival of MSCs. While the HCMN virus infects between 50 percent and 80 percent of people in the U.S., it normally produces no symptoms and remains latent in the body over long periods.

"We wanted to take advantage of the virus' ability to evade the immune system," said Almeida-Porada. "Our strategy was to modify the cells to produce the same proteins as the HCMV virus so they could escape death and help modulate inflammation and promote healing."

MSCs were purified from human fetal liver tissue. They were then engineered to produce specific proteins expressed by the HMCV virus. Through this process, the scientists identified the protein that was most effective at increasing cell survival. Specifically, the team is the first to show that overexpression of the US2 protein made the cells less recognizable to the immune system and increased cell survival by 59 percent (+/- 13 percent).

"The research showed that modifying the cells indeed improves their survival," said Almeida-Porada. "Next, we hope to evaluate the healing potential of these cells in conditions such as bowel disease, traumatic brain injury and human organ transplant."

### The research was supported by National Institutes of Health grants HL73737 and HL97623.

Almeida-Porada's co-researchers were Melisa A. Soland, Ph.D., and Christopher Porada, Ph.D., Wake Forest Baptist; Mariana Bego, Ph.D., Institut de Recherches Cliniques de Montreal, Canada; and Evan Colletti, Ph.D, Esmail Zanjani, Ph.D., and Stephen S. Jeor, Ph.D., University of Nevada. Media contacts: Karen Richardson
Media Relations Office
336-716-4587.

Wake Forest Baptist Medical Center is a fully integrated academic medical center located in Winston-Salem, North Carolina. The institution comprises the medical education and research components of Wake Forest School of Medicine, the integrated clinical structure and consumer brand Wake Forest Baptist Health, which includes North Carolina Baptist Hospital and Brenner Children's Hospital, the creation and commercialization of research discoveries into products that benefit patients and improve health and wellness, through Wake Forest Innovations, Wake Forest Innovation Quarter, a leading center of technological discovery, development and commercialization, as well as a network of affiliated community-based hospitals, physician practices, outpatient services and other medical facilities. Wake Forest School of Medicine is ranked among the nation's best medical schools and is a leading national research center in fields such as regenerative medicine, cancer, neuroscience, aging, addiction and public health sciences. Wake Forest Baptist's clinical programs have consistently ranked as among the best in the country by U.S. News & World Report for the past 20 years. END