UNMC to begin using Bush-approved embryonic stem cell lines

Two UNMC research teams will soon be receiving training on how to use embryonic stem cell lines in their research and will be bringing the cell lines back to UNMC following their training. The embryonic stem cell lines that will be used are among the stem cell lines approved by President Bush.

The two UNMC research teams are headed by Ira Fox, M.D., Charles W. McLaughlin Professor of Surgery and associate dean for research and development in the UNMC College of Medicine, and Stephen Rennard, M.D., Larson Professor of Pulmonary Medicine. Two people on each team will receive training in the use of embryonic stem cells in research.

Dr. Fox's team will be going to the University of Wisconsin in Madison in mid-February to receive their training, while Dr. Rennard will be going to the University of California at San Francisco in March and his associate, Xiangde "Martin" Liu, M.D., Ph.D., will be going to the University of Wisconsin in April.

"We are excited and proud to enter the embryonic stem cell research arena," said Thomas Rosenquist, Ph.D., vice chancellor for research. "We have been a leader in the study of adult stem cells and other research methods, and we believe that embryonic stem cell research may have even more potential to benefit mankind.

"Advances in biomedical research in the first 50 years of the 21st century will be based upon advances in stem cell technology. UNMC must be part of this advance, or we will be left behind. The issue is so important that, in several states, the legislatures have passed, or are considering, bills to support centers of embryonic stem cell research."

A liver transplant surgeon, Dr. Fox is trying to determine if embryonic stem cells can be turned into liver cells that can be infused into a diseased liver to correct liver failure. Due to the shortage of organ donors to meet the increased demand for organ transplants, Dr. Fox has devoted his research over the past decade to looking at alternative ways - other than organ transplantation - to regenerate damaged liver cells. During this period, Dr. Fox has studied adult stem cells and pig liver cells for this purpose.

Infusing human liver cells into a diseased liver in 1997, Dr. Fox was the first to get the cells to function for more than a year and partially correct a patient's rare metabolic liver disease. In doing so, the patient was able to avoid undergoing a liver transplant. The research was reported in the New England Journal of Medicine in May 1998.

"Things have changed over the past few years," Dr. Fox said. "It's unlikely that we will ever be able to get human liver cells in the quantity we need to do more than a couple liver cell infusions a year. Although somewhat damaged, the liver we used in our previous research would more than likely be used for an organ transplant today. That's a measure of how great the organ donor shortage is.

"Science is moving quickly into the regenerative medicine field. Many scientists are trying to use stem cells to regenerate diseased tissue. It's an exciting area of investigation."

Dr. Fox plans to infuse his embryonic stem cell-derived liver cells into two animal models. One of these is a special mouse model that has been generated to provide human liver cells a growth advantage over the native liver cells of the mouse. The other is an animal model with liver failure in which transplantation of human liver cells can correct the disease process.

Dr. Fox said, "We will transplant the embryonic stem cell-derived liver cells into these animal models and see if they will engraft into the liver and possibly correct the diseased tissue."

"We need this seed money to allow us to conduct research and develop preliminary data," Dr. Fox said. "Once we get this preliminary data, we will use the results to procure a federal grant. If we are going to compete with other medical centers around the country for federal grants, it's imperative that we generate such preliminary data. The federal government does not provide seed money for exploratory work and new concept development. It supports research that has been shown to be viable based on preliminary studies."

As announced last summer, Dr. Rennard was asked by the National Institutes of Health to apply for a grant to study emphysema using embryonic stem cells. He recently learned, however, that his grant proposal will not be funded by the NIH.

Dr. Rennard's research has determined that the cells responsible for healing appear to be abnormal in lungs with emphysema and chronic obstructive pulmonary disease (COPD). He theorizes that the infusion of stem cells could help the healing cells in the lung to grow new tissue.

Dr. Rennard and his team, Dr. Liu and J. Graham Sharp, Ph.D., previously have shown that mouse stem cells injected into mice go to the lung, differentiate or change, and form cells called fibroblasts which make up the connective tissue in the lungs and other parts of the body. Currently, it is unknown if mouse and human cells behave similarly in this process.

"Understanding how stem cells are directed to form new lung tissue offers great promise to treat lung diseases such as emphysema," Dr. Rennard said.

The entire cost of conducting these two embryonic stem cell research projects will paid for with non-state sources, Dr. Rosenquist said.

Before these research projects can be conducted, they were approved by UNMC's Institutional Review Board, the Institutional Animal Care and Use Committee and an internal scientific review panel as required in the recommendations for Human Stem Cell Research developed by the University of Nebraska Bioethics Advisory Committee.